Sacituzumab Govitecan in Hormone

rapid communications Receptor–Positive/Human Epidermal Growth

Factor Receptor 2–Negative Metastatic
Breast Cancer
Hope S. Rugo, MD1; Aditya Bardia, MD, MPH2; Frederik Marmé, MD, PhD3; Javier Cortes, MD, PhD4,5; Peter Schmid, MD, PhD6;
Delphine Loirat, MD, PhD7; Olivier Trédan, MD, PhD8; Eva Ciruelos, MD, PhD9; Florence Dalenc, MD, PhD10; Patricia Gómez Pardo, MD11;
Komal L. Jhaveri, MD12; Rosemary Delaney, MPH13; Olivia Fu, MD14; Lanjia Lin, PhD15; Wendy Verret, PhD13; and
Sara M. Tolaney, MD, MPH16; on behalf of the TROPiCS-02 Study Investigators
abstract

PURPOSE Hormone receptor–positive (HR1) human epidermal growth factor receptor 2–negative (HER2–)
endocrine-resistant metastatic breast cancer is treated with sequential single-agent chemotherapy with poor
outcomes. Sacituzumab govitecan (SG) is a first-in-class antibody-drug conjugate with an SN-38 payload
targeting trophoblast cell-surface antigen 2, an epithelial antigen expressed in breast cancer.
METHODS In this global, randomized, phase III study, SG was compared with physician’s choice chemotherapy
(eribulin, vinorelbine, capecitabine, or gemcitabine) in endocrine-resistant, chemotherapy-treated HR1/HER2–
locally recurrent inoperable or metastatic breast cancer. The primary end point was progression-free survival
(PFS) by blinded independent central review.
RESULTS Patients were randomly assigned to receive SG (n 5 272) or chemotherapy (n 5 271). The median age
was 56 years, 95% had visceral metastases, and 99% had a prior cyclin-dependent kinase 4/6 inhibitor, with
three median lines of chemotherapy for advanced disease. Primary end point was met with a 34% reduction in
risk of progression or death (hazard ratio, 0.66 [95% CI, 0.53 to 0.83; P 5 .0003]). The median PFS was
5.5 months (95% CI, 4.2 to 7.0) with SG and 4.0 months (95% CI, 3.1 to 4.4) with chemotherapy; the PFS at 6 and
12 months was 46% (95% CI, 39 to 53) v 30% (95% CI, 24 to 37) and 21% (95% CI, 15 to 28) v 7% (95% CI, 3 to
14), respectively. Median overall survival (first planned interim analysis) was not yet mature (hazard ratio, 0.84;
P 5 .14). Key grade $ 3 treatment-related adverse events (SG v chemotherapy) were neutropenia (51% v 38%)
and diarrhea (9% v 1%).
CONCLUSION SG demonstrated statistically significant PFS benefit over chemotherapy, with a manageable safety
profile in patients with heavily pretreated, endocrine-resistant HR1/HER2– advanced breast cancer and limited
treatment options.

J Clin Oncol 00. © 2022 by American Society of Clinical Oncology

ASSOCIATED Creative Commons Attribution Non-Commercial No Derivatives 4.0 License
CONTENT
Appendix INTRODUCTION Sacituzumab govitecan (SG) is a first-in-class trophoblast
Data Supplement Although endocrine therapy combined with cyclin- cell-surface antigen 2 (Trop-2)–directed antibody-drug
Protocol dependent kinase 4/6 inhibitors (CDK4/6i) has ex- conjugate (ADC), consisting of a humanized anti–
Author affiliations Trop-2 monoclonal antibody conjugated to the ac-
tended overall survival (OS) for metastatic hormone
and support tive metabolite of irinotecan, SN-38,11 via a hydro-
information (if receptor–positive (HR1) human epidermal growth factor
lyzable CL2A linker.12 Trop-2 is a transmembrane
applicable) appear receptor 2–negative (HER2–) breast cancer to over
calcium signal transducer highly expressed in solid
at the end of this 5 years in the first-line setting1-5 and combinations with
article. tumors, especially HR1/HER2– and triple-negative
phosphoinositide 3-kinase or mammalian target of breast cancers (with a prevalence of . 90%), and
Accepted on July 28,
2022 and published at rapamycin inhibitors offer benefit in subsequent treat- linked to tumor progression and poor prognosis.13-15
ascopubs.org/journal/ ment lines,6 endocrine resistance eventually develops. Internalization of Trop-2–bound SG delivers SN-38
jco on August 26, Sequential single-agent chemotherapy is the next ther-
2022: DOI https://doi.
into the tumor cell through hydrolysis of the linker.16
org/10.1200/JCO.22. apeutic option but is associated with declining response Because SN-38 is a membrane-permeable free
01002 rates and disease control and increased toxicity.6-10 molecule released in the tumor microenvironment, it

1
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 Rugo et al

CONTEXT
Key Objective
Hormone receptor–positive (HR1) human epidermal growth factor receptor 2–negative (HER2–) breast cancer is treated
with sequential endocrine therapy combined with targeted agents, followed by sequential single-agent chemotherapy,
with declining response rates and increased toxicity. This randomized, global phase III study evaluates sacituzumab
govitecan (SG), a trophoblast cell-surface antigen 2–directed antibody-drug conjugate, versus single-agent chemo-
therapy in HR1/HER2– advanced breast cancer.
Knowledge Generated
SG demonstrated a significant improvement in progression-free survival over chemotherapy (median, 5.5 months v 4.0
months; hazard ratio, 0.66; P 5 .0003) in patients who have received prior endocrine-based therapy, including cyclin-
dependent kinase 4/6 inhibitors and $ 2 prior chemotherapy regimens in the metastatic setting. The SG safety profile
was manageable and consistent with previous studies, with neutropenia and diarrhea as the most common treatment-
related adverse events.
Relevance (K.D. Miller)
SG is a treatment option for patients with heavily pretreated, endocrine-resistant HR1/HER2– advanced breast cancer.*
*Relevance section written by JCO Senior Deputy Editor Kathy D. Miller, MD.

may elicit antitumor effects in adjacent non–Trop-2- one anticancer hormonal treatment, and at least one CDK4/
expressing tumor cells (bystander effect).16 6i, reflecting standard clinical practice. Additional details
SG received full authorization from the Food and Drug are provided in the Data Supplement.
Administration and European Medicines Agency for Trial Design and Treatment
patients with metastatic triple-negative breast cancer
who had received at least two prior chemotherapies (at Patients were randomly assigned 1:1 to receive 10 mg/kg of
least one for metastatic disease) and has accelerated SG (Trodelvy; Gilead Sciences Inc, Foster City, CA) intra-
approval for locally advanced or metastatic urothelial venously once weekly on day 1 and day 8 every 21 days or
cancer.17-19 In the phase I/II IMMU-132-01 basket study, chemotherapy of physician’s choice determined before
SG showed encouraging activity and safety in 54 patients random assignment (eribulin, capecitabine, gemcitabine,
with HR1/HER2– metastatic breast cancer (MBC) who or vinorelbine). The chemotherapy agents included in this
progressed on at least one line of endocrine therapy and trial, and their recommended doses, were in accordance
at least one prior chemotherapy in the metastatic set- with locally approved prescribing information or according
ting.20 The objective response rate was 31.5%, and the to National Comprehensive Cancer Network Clinical
median progression-free survival (PFS) and OS were 5.5 Practice Guidelines in Oncology (National Comprehensive
and 12 months, respectively (CDK4/6i-pretreated group, Cancer Network Guidelines) for Breast Cancer.21 Recom-
25%, 3.8 and 11 months). mended doses are summarized below: eribulin, 1.4 mg/m2
Here, we provide the primary results of TROPiCS-02, a (North America) or 1.23 mg/m2 (Europe) intravenously
global, randomized, open-label, multicenter phase III study once weekly on days 1 and 8 every 21 days; vinorelbine,
of SG versus single-agent chemotherapy in patients with 25 mg/m2 intravenously once weekly; gemcitabine, 800-1,
locally recurrent inoperable or metastatic HR1/HER2– 200 mg/m2 intravenously once weekly on days 1, 8, and 15
breast cancer (Data Supplement, online only). every 28 days; and capecitabine, 1,000-1,250 mg/m2 orally
twice daily for 2 weeks followed by a 1 week rest period,
every 21 days.
METHODS
Random assignment was stratified by number of prior
Patients chemotherapy regimens for metastatic disease, visceral
Eligible patients had histologically locally confirmed mea- metastases, and prior endocrine treatment in the meta-
surable HR1/HER2– MBC and 2-4 prior systemic che- static setting for at least 6 months. Patients were treated
motherapy regimens for metastatic disease. (Neo)adjuvant until disease progression, unacceptable toxicity, withdrawal
therapy for early-stage disease qualified as one of the re- of consent, or per investigator’s decision that it was in the
quired prior chemotherapy regimens if the development of patient’s best interest to discontinue. Treatment beyond
unresectable, locally advanced, or metastatic disease oc- progression was permitted if deemed clinically beneficial by
curred within 12 months of therapy (early relapse). Patients the investigator. Additional details are provided in the Data
must have previously received at least one taxane, at least Supplement.

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 Sacituzumab Govitecan in HR+/HER2– Metastatic Breast Cancer

Trial Oversight The intent-to-treat population includes all randomly

The study was approved by national regulatory authorities assigned patients (efficacy population). Stratification fac-
and each investigational site’s institutional review/ethics tors used in random assignment were applied to all strat-
committee before implementation and was compliant ified analyses. All patients who received at least one dose of
with the Declaration of Helsinki and International Council study drug were included in safety analyses. Additional
for Harmonisation Good Clinical Practice Guidelines. All details are provided in the Data Supplement.
patients provided written informed consent.
RESULTS
End Points
Patient Characteristics
The primary end point was PFS as determined by blinded
independent central review (BICR) per the RECIST v1.1.22 From May 2019 to April 2021, 543 patients with HR1/HER2–
Secondary end points included OS, objective response, locally inoperable or MBC were enrolled in 91 centers across
clinical benefit rate, duration of response, patient-reported North America (United States and Canada) and Europe (the
outcomes, and safety (Data Supplement). United Kingdom, France, Spain, Italy, Germany, Belgium, and
the Netherlands). Patients were randomly assigned to the SG
Assessments group (272 patients) or chemotherapy group (271 patients;
The primary and secondary end points were measured by 48% eribulin, 23% vinorelbine, 21% gemcitabine, and 8%
computed tomography or magnetic resonance imaging, capecitabine; Data Supplement). In total, 268 patients (99%)
conducted every 6 weeks for the first 54 weeks and every in the SG group and 249 patients (92%) in the chemotherapy
12 weeks thereafter. Additional details are provided in the group received study treatment. Of the 26 patients randomly
Data Supplement. assigned but not treated, 16 withdrew consent (one for SG and
15 for chemotherapy).
Safety and tolerability were assessed in all treated patients
throughout the study, with severity of adverse events (AEs) The median age was 56 years (range, 27-86; Table 1). Most
graded using National Cancer Institute Common Termi- had visceral metastases (95%) and received endocrine
nology Criteria for Adverse Events v5.0. Patients were therapy in the metastatic setting for at least 6 months (86%);
allowed premedications (eg, antipyretics and H1 blockers) 40% of patients received CDK4/6i therapy for more than 12
for prevention of infusion reactions and supportive medi- months. Patients received a median of 3 (range, 0-8) prior
cations for the prevention and treatment of chemotherapy- lines of chemotherapy in the metastatic setting (57% at least
induced nausea, vomiting, and diarrhea. three lines). At the data cutoff date (January 3, 2022), 18
patients (7%) in the SG group and four (1.5%) in the che-
Statistical Analysis motherapy group remained on study treatment. Patients
Anticipated recruitment was 520 patients; sample size discontinued study treatment primarily because of progressive
calculation was based on treatment group comparisons, disease (SG group, 77%; chemotherapy group, 73%; Fig 1).
with PFS as the primary end point and OS as the key Efficacy
secondary end point. For PFS, assuming a hazard ratio
(HR) of 0.70, 350 events of progression or death were As of the data cutoff date, the median duration of follow-up
needed to detect a statistically significant PFS difference was 10.2 months (11.3 months with SG and 9.8 months
between treatment groups at a two-sided a of .05 with 92% with chemotherapy). The primary end point of PFS was met
power. For OS, assuming a HR of 0.73, 438 events were with a 34% reduction in risk of progression or death (HR,
needed to detect a statistically significant difference with 0.66; 95% CI, 0.53 to 0.83; P 5 .0003; 329 events); the
87% power at a two-sided a of .05. OS would be formally median PFS determined by BICR was 5.5 months (95% CI,
tested sequentially if PFS is statistically significant, and then 4.2 to 7.0) for SG and 4.0 months (95% CI, 3.1 to 4.4) for
objective response and quality of life (QoL) if the prior end chemotherapy (Fig 2A and Table 2). The reduction in risk of
point in the hierarchy is significant. The study was planned progression or death was consistent with local investigator
to have two interim analyses and a final analysis of OS, with assessment (HR, 0.73; 95% CI, 0.60 to 0.88; P 5 .001;
272 events targeted for the first interim and .036 a to be Data Supplement).
spent on the basis of Lan DeMets a spending function that In landmark analyses, the PFS rates at 6 and 12 months
approximated a Pocock approach. Analysis of OS was (SG v chemotherapy) were 46% versus 30% and 21%
combined with the primary PFS analysis since the required versus 7%, respectively (Fig 2A and Table 2). The PFS
OS events for the first interim analysis were reached earlier benefit for SG over chemotherapy was maintained in most
than PFS events (329 events occurred). predefined subgroups, including patients with three or
AEs summarized were treatment-emergent unless other- more prior chemotherapy regimens in the metastatic set-
wise specified (defined as any AEs that began or worsened ting, visceral metastases, and age 65 years or older (Fig 3).
on or after study drug administration through 30 days after Because PFS results were statistically significant, OS was
the last dose of study drug). sequentially tested. The median OS (first planned interim

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 Rugo et al

TABLE 1. Baseline Characteristics and Treatment History of Patients

Characteristic SG (n 5 272) Chemotherapy (n 5 271) All (N 5 543)
Female, No. (%) 270 (99) 268 (99) 538 (99)
Median age, years (range) 57 (29-86) 55 (27-78) 56 (27-86)
Race or ethnic group, No. (%)
White 184 (68) 178 (66) 362 (67)
Black 8 (3) 13 (5) 21 (4)
Asian 11 (4) 5 (2) 16 (3)
a
Others 0 5 (2) 5 (1)
Not specifiedb 69 (25) 70 (26) 139 (26)
ECOG PS, No. (%)
0 116 (43) 126 (46) 242 (45)
1 156 (57) 145 (54) 301 (55)
Visceral metastases at baseline, No. (%) 259 (95) 258 (95) 517 (95)
Liver metastases,c No. (%) 229 (84) 237 (87) 466 (86)
De novo MBC, No. (%) 78 (29) 60 (22) 138 (25)
Median time from initial metastatic diagnosis to random assignment, months (range) 48.5 (1.2-243.8) 46.6 (3.0-248.8) 47.8 (1.2-248.8)
Prior chemotherapy in the (neo)adjuvant setting, No. (%) 173 (64) 184 (68) 357 (66)
Prior endocrine therapy in the metastatic setting . 6 months, No. (%)
Yes 235 (86) 234 (86) 469 (86)
No 37 (14) 37 (14) 74 (14)
Prior CDK4/6i use, months, No. (%)
# 12 161 (59) 166 (61) 327 (60)
. 12 106 (39) 102 (38) 208 (38)
Unknown 5 (2) 3 (1) 8 (1)
Median prior chemotherapy regimens in the metastatic setting, No. (%)d 3 (0-8)d 3 (1-5)d 3 (0-8)d
0 1 (, 1) 0 1 (, 1)
1 8 (3) 2 (1) 10 (2)
2 104 (38) 118 (43) 222 (41)
$3 159 (58) 151 (56) 310 (57)
Median prior chemotherapy regimens, No. (range) 4 (1-9) 4 (2-7) 4 (1-9)
e
Median prior anticancer regimens, No. (range) 7 (3-17) 7 (3-16) 7 (3-17)
Setting of prior anticancer regimens,e No. (%)
Neoadjuvant 67 (25) 62 (23) 129 (24)
Adjuvant 186 (68) 206 (76) 392 (72)
Advanced/metastatic 272 (100) 271 (100) 543 (100)
Others/unknown 12 (4) 9 (3) 21 (4)
Most common prior anticancer therapy,e No. (%)
Palbociclib 238 (88) 228 (84) 466 (86)
Capecitabine 226 (83) 234 (86) 460 (85)
Fulvestrant 235 (86) 223 (82) 458 (84)
Cyclophosphamide 204 (75) 209 (77) 413 (76)
Paclitaxel 210 (77) 196 (72) 406 (75)
Letrozole 185 (68) 210 (77) 395 (73)
Tamoxifen 160 (59) 165 (61) 325 (60)
(continued on following page)

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 Sacituzumab Govitecan in HR+/HER2– Metastatic Breast Cancer

TABLE 1. Baseline Characteristics and Treatment History of Patients (continued)

Characteristic SG (n 5 272) Chemotherapy (n 5 271) All (N 5 543)
e
Doxorubicin 149 (55) 134 (49) 283 (52)
Exemestane 142 (52) 134 (49) 276 (51)
Everolimus 117 (43) 115 (42) 232 (43)
Docetaxel 106 (39) 120 (44) 226 (42)
e
Eribulin 97 (36) 97 (36) 194 (36)
Anastrozole 87 (32) 69 (25) 156 (29)
Epirubicin 78 (29) 94 (35) 172 (32)
Fluorouracil 66 (24) 77 (28) 143 (26)
Most common prior anticancer therapy class in the metastatic setting,e No. (%)
Endocrine therapy 268 (99) 269 (99) 537 (99)
CDK4/6i 267 (98) 270 (. 99) 537 (99)
Targeted agent 181 (67) 172 (63) 353 (65)
Immunotherapy 21 (8) 15 (6) 36 (7)
Chemotherapy 271 (. 99) 271(100) 542 (. 99)
Most common prior chemotherapy agent in the metastatic setting,e No. (%)
Capecitabine 221 (81) 232 (86) 453 (83)
Paclitaxel 174 (64) 147 (54) 321 (59)
Eribuline 95 (35) 88 (33) 183 (34)
f
ER expression, No. (%)
, 1% 2 (1) 5 (2) 7 (1)
1%-10% 12 (4) 15 (6) 27 (5)
. 10% 258 (95) 246 (91) 504 (93)
Unknown 0 5 (2) 5 (1)
f
PR expression, No. (%)
, 1% 103 (38) 101 (37) 204 (38)
1%-10% 45 (17) 44 (16) 89 (16)
. 10% 124 (46) 120 (44) 244 (45)
Unknown 0 6 (2) 6 (1)

Abbreviations: CDK4/6i, cyclin-dependent kinase 4/6 inhibitor; ECOG PS, Eastern Cooperative Oncology Group performance status; ER, estrogen receptor;
MBC, metastatic breast cancer; PR, progesterone receptor; SG, sacituzumab govitecan.
a
Includes American Indian or Alaska Native, Native Hawaiian or other Pacific Islander.
b
Not reported indicates local regulators who did not allow collection of race or ethnicity information.
c
Presence of baseline target/nontarget liver lesion per RECIST1.1 by local investigator review.
d
The reported number of prior therapies was miscounted at screening for some patients. Nine patients had fewer or more prior chemotherapy regimens in
the metastatic setting than the specified inclusion criteria and were included in the intention-to-treat population.
e
Anticancer regimens refer to any treatment regimen that was used to treat breast cancer in any setting and includes endocrine therapy and everolimus.
Eribulin includes the preferred drug name eribulin and eribulin mesylate. Doxorubicin includes the preferred drug name doxorubicin, pegylated liposomal
doxorubicin hydrochloride, liposomal doxorubicin, doxorubicin hydrochloride, liposomal doxorubicin hydrochloride, and pegylated liposomal doxorubicin.
f
Per protocol, hormone receptor status was to be documented from locally recurrent or metastatic sites and the few cases that did not have protocol
deviations.

analysis) was 13.9 months (95% CI, 12.7 to 15.4) for SG The percentage of patients with objective response by BICR
and 12.3 months (95% CI, 10.8 to 14.2) for chemotherapy was 21% with SG and 14% with chemotherapy (Table 2), of
(HR for death, 0.84; 95% CI, 0.67 to 1.06; P 5 .14; Fig 2B). which two patients (1%) and no patients achieved a
These results are not yet mature; further follow-up is on- complete response, respectively. Clinical benefit rate was
going. Because OS was not significant, objective response higher with SG than with chemotherapy (34% v 22%). The
and QoL end points—which fell after OS in the hierarchy— median time to response was 2.9 (range, 1.2-11.3) months
were not formally tested. with SG and 2.7 (range, 1.2-10.5) months with

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 Rugo et al

Patients Screened
(N = 776)

Patients Randomized
(N = 543)

Sacituzumab Govitecan Group Chemotherapy Groupa

(n = 272) (n = 271)

Treatment not received (n = 4) Treatment not received (n = 22)

Safety Population Safety Population Discontinuations (n = 245)

Discontinuations (n = 250) (n = 268) (n = 249) Progressive disease (n = 197)
Progressive disease (n = 210) Consent withdrawal (n = 22)
Adverse events (n = 18) Adverse events (n = 11)
Consent withdrawal (n = 8) Other (n = 6)
Treatment delay > 3 wk (n = 5) Protocol deviation (n = 3)
Other (n = 5) Remain On Treatment Remain On Treatment (non-compliance)
Death (n = 3) (n = 18) (n = 4) COVID-19 disease (n = 3)
Protocol deviation (n = 1) Death (n = 2)
(non-compliance) Treatment delay > 3 wk (n = 1)

FIG 1. CONSORT diagram. aPatients in the chemotherapy group were randomly assigned to eribulin (n 5 130), vinorelbine (n 5 63), gemcitabine (n 5 56), or
capecitabine (n 5 22). AE, adverse event; SG, sacituzumab govitecan.

chemotherapy. The median duration of response was was a low incidence of treatment-related febrile neu-
7.4 months (95% CI, 6.5 to 8.6) with SG and 5.6 months tropenia (5% v 4%), interstitial lung disease (0% v 1%), and
(95% CI, 3.8 to 7.9) with chemotherapy. neuropathy (9% v 15%). For additional results about
growth factor use, see the Data Supplement.
For patient-reported outcomes, the European Organiza-
tion for Research and Treatment of Cancer QoL ques- Given the difference in treatment durations in the SG and
tionnaire completion rate was at least 85% through cycle chemotherapy groups, a summary of exposure-adjusted
13 day 1 for both SG and chemotherapy and was generally incidence rates (EAIRs) for AEs is provided in the Data
comparable across assessments between treatment groups. Supplement. Although the EAIRs for common AEs of any
Median time to deterioration was longer for SG versus che- grade, such as diarrhea, alopecia, and nausea, were
motherapy for global health status/QoL (4.0 v 2.9 months; HR, higher with SG versus chemotherapy, the EAIRs for other
0.74; 95% CI, 0.59 to 0.91) and fatigue (2.1 v 1.4 months; common AEs of any grade, including neutropenia, ane-
HR, 0.76; 95% CI, 0.62 to 0.93). Median time to deterioration mia, and fatigue, were similar between treatment groups
for pain was similar (3.7 v 3.4 months; HR, 0.92; 95% CI, 0.74 (EAIR difference [95% CI]: diarrhea: 2.29 per patient-
to 1.14). years of exposure [PYE; 1.72 to 2.87], alopecia: 1.23 per
PYE [0.80 to 1.68]; nausea: 0.85 per PYE [0.30 to 1.39];
Safety neutropenia: 0.75 per PYE [–0.16 to 1.66]; anemia: 0 per
In the safety population, the median duration of treatment PYE [–0.37 to 0.35]; fatigue: –0.36 per PYE [–0.82 to
was 4.1 (range, 0.03-24.2) months and 2.3 (range, 0.03- 0.07]).
22.3) months with SG and chemotherapy, respectively.
Serious treatment-related AEs were reported in 37 patients
Patients in the SG group received a mean of 8.2 treatment
(14%) in the SG group and 25 patients (10%) in the
cycles (range, 1.0-35.0), with a median relative dose in-
chemotherapy group. The most common ($ 2% incidence)
tensity of 99%.
serious treatment-related AEs for SG were diarrhea (5%),
An AE summary is found in the Data Supplement. The most febrile neutropenia (4%), neutropenia (3%), and neu-
common treatment-related AEs of any grade (. 25% in- tropenic colitis (2%); for chemotherapy, they were febrile
cidence) with SG versus chemotherapy were neutropenia neutropenia (4%), pneumonia (2%), nausea (2%), and
(70% v 54%), diarrhea (57% v 16%), nausea (55% v dyspnea (2%). AEs leading to study treatment discontin-
31%), alopecia (46% v 16%), fatigue (37% v 29%), and uations occurred in 17 patients (6%) in the SG group and
anemia (34% v 25%). The most common grade 3 or higher 11 patients (4%) in the chemotherapy group. Dose delays
treatment-related AEs (. 5% incidence) were neutropenia and reductions can be found in the Data Supplement.
(51% v 38%), leukopenia (9% v 5%), diarrhea (9% v 1%), Although six patients experienced AEs leading to death in
anemia (6% v 3%), and fatigue (6% v 2%; Table 3). There the SG group, only one had a treatment-related AE leading

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 Sacituzumab Govitecan in HR+/HER2– Metastatic Breast Cancer

A
Sacituzumab govitecan Chemotherapy
(n = 272) (n = 271)
No. of events 170 159

100 PFS rate

6 mo 46% 30%
90 12 mo 21% 7%
Median PFS
80 —mo (95% CI) 5.5 (4.2 to 7.0) 4.0 (3.1 to 4.4)
70 HR (95% CI), P-value 0.66 (0.53 to 0.83), P = .0003

PFS (%)
60 Sacituzumab govitecan
50 Chemotherapy

40
30
20
10

0 3 6 9 12 15 18 21 24

Time (months)
No. at risk:
Sacituzumab govitecan 272 148 82 44 22 12 6 3 0
Chemotherapy 271 105 41 17 4 1 1 0

B
Sacituzumab govitecan Chemotherapy
(n = 272) (n = 271)
100 No. of events 149 144
90 Median OS
—mo (95% CI) 13.9 (12.7 to 15.4) 12.3 (10.8 to 14.2)
80 HR (95% CI), P-value 0.84 (0.67 to 1.06), P = .14
70
60
OS (%)

50
40
30
20
Sacituzumab govitecan
10 Chemotherapy

0 3 6 9 12 15 18 21 24 27 30

Time (months)
No. at risk:
Sacituzumab govitecan 272 247 215 183 123 77 47 29 7 2 0
Chemotherapy 271 224 177 150 96 56 35 20 5 0

FIG 2. Efficacy outcomes in the intent-to-treat population. (A and B) PFS (final analysis) and OS (first planned interim
analysis), respectively, in the intent-to-treat population (all randomly assigned patients). PFS was determined by
blinded independent central review according to RECIST, version 1.1. HR, hazard ratio; OS, overall survival; PFS,
progression-free survival; SG, sacituzumab govitecan.

to death (septic shock because of neutropenic colitis). The DISCUSSION

AEs leading to death in the remaining five patients included Patients with metastatic HR1/HER2– breast cancer ul-
(n 5 1 each) arrhythmia, COVID-19 pneumonia, pulmo- timately develop endocrine resistance, and treatment
nary embolism, pneumonia, and nervous system disorder. options are limited to sequential single-agent chemo-
The patients with fatal infections of COVID-19 pneumonia therapy. In this phase III trial of patients with heavily
and pneumonia were not neutropenic at the time of event pretreated, locally recurrent inoperable, or metastatic
onset. No mechanistic or etiologic pattern was identified for HR1/HER2– breast cancer, SG, a Trop-2–directed ADC,
these AEs (Data Supplement). No AEs leading to death demonstrated significant improvement in PFS versus
were reported in the chemotherapy group. chemotherapy with a 34% reduction in risk of disease

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 Rugo et al

TABLE 2. Summary of Treatment Efficacy (per blinded independent central review)

Efficacy Outcome SG (n 5 272) Chemotherapy (n 5 271)
Median PFS, months (95% CI), 5.5 (4.2 to 7.0) 4.0 (3.1 to 4.4)
HR; P (95% CI) 0.66 (0.53 to 0.83); P 5 .0003
PFS rate, %, months (95% CI)
6 46 (39 to 53) 30 (24 to 37)
12 21 (15 to 28) 7 (3 to 14)
Median OS, months (95% CI) 13.9 (12.7 to 15.4) 12.3 (10.8 to 14.2)
HR; P (95% CI) 0.84 (0.67 to 1.06); P 5 .14
Objective response rate, No. (%) 57 (21) 38 (14)
Best overall response, No. (%)
Complete response 2 (1) 0
Partial response 55 (20) 38 (14)
Stable disease 142 (52) 106 (39)
Stable disease $ 6 months 35 (13) 21 (8)
Progressive disease 58 (21) 76 (28)
Not evaluable 15 (6) 51 (19)
a
CBR, No. (%) 92 (34) 59 (22)
Median DOR, months (95% CI) 7.4 (6.5 to 8.6) 5.6 (3.8 to 7.9)

Abbreviations: CBR, clinical benefit rate; DOR, duration of response; HR, hazard ratio; OS, overall survival; PFS, progression-free survival; SG, sacituzumab
govitecan.
a
CBR is defined as the percentage of patients with a confirmed best overall response of complete response, partial response, and stable disease $ 6
months.

progression or death (HR, 0.66; P 5 .0003) and a higher demonstrated a significant PFS improvement (4.1 v 3.4
proportion of patients who are alive and progression-free months; HR, 0.84; P 5 .03) with eribulin, but no significant
at all landmark time points with nonoverlapping confi- OS benefit (15.7 v 13.5 months; HR, 0.87; P 5 .06) versus
dence intervals compared with chemotherapy. other chemotherapies in patients with HR1 MBC.25 Com-
parison with this pooled analysis is complicated by the fact
The population in this study had progressive disease and
that these two studies involved different patient populations
extensive prior chemotherapy treatment in the advanced
with regard to the extent of prior chemotherapy for advanced
setting (median prior lines of chemotherapy 5 3), and
disease (eligibility, EMBRACE: 2-5; Study 301: up to 2),
uniquely, all patients had received prior CDK4/6i, reflecting
HER2 status, and lack of prior use of CDK 4/6i.
standard of care and allowing assessment of efficacy post-
CDK4/6i treatment. Recently, the phase III DESTINY-Breast04 trial compared
the ADC trastuzumab deruxtecan with chemotherapy of
Benefit with SG was seen across most of the prespecified
physician’s choice in a patient population that partially
subgroups, including patients who received at least three
prior chemotherapies for metastatic disease, had visceral overlaps with those enrolled in TROPiCS-02. Trastuzumab
metastases, and were age 65 years or older. The OS re- deruxtecan significantly improved both PFS and OS in pa-
sults (16% reduction in risk of death; P 5 .14) are not yet tients with HR1/HER2-low MBC;26 however, there are im-
mature in the first planned interim analysis. Overall, re- portant differences in the study populations that limit
sults are consistent with those from the HR1/HER2– comparisons with this trial. DESTINY-Breast04 only included
cohort of the phase I/II IMMU-132-01 basket study,20 and patients with HER2-low (immunohistochemistry 11 or im-
performance of the control group is as previously munohistochemistry 21/in situ hybridization-negative) less
reported.6-10 Additional preplanned follow-up will provide heavily pretreated disease (median number of prior che-
more clarity into the survival benefit of SG in this patient motherapies in the metastatic setting 5 1), along with other
population. differences. It is clear that the standard of care now includes
treatment with ADCs for a number of breast cancer subtypes;
With limited advancements for treatments in this later-line
sequential efficacy is yet to be evaluated.
setting, the most recent phase III trials in a similar patient
population were EMBRACE,8 which led to the approval of SG demonstrated a manageable safety profile, with a low
eribulin in 2010,23 and Study 301.24 A pooled analysis incidence of treatment discontinuation because of AEs

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 Sacituzumab Govitecan in HR+/HER2– Metastatic Breast Cancer

PFS
Median Months (95% Cl)
Subgroup Sacituzumab govitecan Chemotherapy HR (95% Cl)
Overall (N = 543) 5.5 (4.2 to 7.0) 4.0 (3.1 to 4.4) 0.66 (0.53 to 0.82)
Visceral Metastasis
Yes (n = 517) 5.5 (4.2 to 7.0) 4.0 (3.1 to 4.4) 0.66 (0.53 to 0.83)
No (n = 26) 9.1 (1.3 to NE) 5.6 (1.6 to NE) 0.78 (0.25 to 2.40)
Endocrine Therapy In The Metastatic Setting
For ≥ 6 Months
Yes (n = 469) 5.6 (4.4 to 7.4) 4.1 (3.1 to 4.4) 0.61 (0.48 to 0.78)
No (n = 74) 3.9 (2.5 to 5.8) 3.5 (1.6 to 7.7) 1.13 (0.61 to 2.07)
Age Group
< 65 years (n = 403) 5.5 (4.1 to 6.9) 4.1 (3.0 to 4.4) 0.69 (0.53 to 0.89)
≥ 65 years (n = 140) 6.7 (4.2 to 9.0) 3.5 (1.7 to 5.6) 0.59 (0.38 to 0.93)
Race
White (n = 362) 5.3 (4.2 to 7.0) 4.2 (3.0 to 4.5) 0.66 (0.51 to 0.86)
Non-white (n = 42) 3.1 (1.5 to 8.5) 4.0 (1.4 to 8.9) 1.23 (0.55 to 2.75)
ECOG Performance Status
0 (n = 242) 5.7 (4.2 to 8.5) 4.1 (2.7 to 5.7) 0.61 (0.44 to 0.86)
1 (n = 301) 5.0 (4.0 to 7.1) 4.0 (2.8 to 4.4) 0.70 (0.53 to 0.94)
Geographic Region
North America (n = 229) 5.5 (4.1 to 7.1) 4.0 (2.3 to 4.4) 0.72 (0.51 to 1.02)
Europe (n = 314) 5.5 (4.1 to 8.3) 4.1 (2.8 to 4.6) 0.62 (0.46 to 0.82)
Prior CDK Inhibitor Duration
≤ 12 months (n = 327) 6.0 (4.6 to 8.3) 4.0 (2.8 to 4.4) 0.59 (0.44 to 0.78)
> 12 months (n = 208) 4.4 (3.3 to 7.0) 4.2 (2.7 to 5.6) 0.77 (0.54 to 1.10)
Investigator Choice Of Chemotherapy
Eribulin (n = 130) 5.5 (4.2 to 7.0) 4.4 (4.0 to 5.6) 0.71 (0.55 to 0.93)
Capecitabine (n = 22) 5.5 (4.2 to 7.0) 5.6 (1.6 to 6.4) 0.91 (0.53 to 1.57)
Gemcitabine (n = 56) 5.5 (4.2 to 7.0) 4.3 (1.7 to 8.8) 0.83 (0.54 to 1.28)
Vinorelbine (n = 63) 5.5 (4.2 to 7.0) 1.5 (1.4 to 1.9) 0.32 (0.22 to 0.47)
Early Relapse
Yes (n = 42) 5.8 (2.7 to NE) 1.4 (1.2 to 1.7) 0.10 (0.04 to 0.28)
No (n = 488) 5.5 (4.2 to 7.0) 4.2 (3.4 to 5.4) 0.72 (0.57 to 0.91)
No. of Prior Chemotherapy In Metastatic Setting
≤ 2 (n = 233) 5.7 (4.2 to 8.3) 4.2 (2.8 to 5.5) 0.62 (0.45 to 0.85)
≥ 3 (n = 310) 5.3 (4.0 to 6.9) 3.7 (2.7 to 4.4) 0.70 (0.52 to 0.95)

0.0625 0.125 0.25 0.5 1 2 4 8 16

Sacituzumab govitecan better Chemotherapy better

FIG 3. Subgroup analysis of PFS. Early relapse is defined as relapse to metastatic disease within 1 year of the end of (neo)adjuvant chemotherapy.
Patients without chemotherapy in the (neo)adjuvant setting are not considered as early relapse. CDK, cyclin-dependent kinase; ECOG PS, Eastern
Cooperative Oncology Group performance status; HR, hazard ratio; NE, not evaluable; PFS, progression-free survival; SG, sacituzumab govitecan.

(6%). The most clinically relevant grade 3 or 4 AEs with SG of prior treatments and chemotherapy of physician’s choice
were neutropenia and diarrhea, adequately managed with options might have affected efficacy findings. Hormone
established supportive care measures, as previously re- receptor status was determined locally at any stage of
ported.27 The incidence of treatment-related febrile disease, which has historically presented challenges for
neutropenia and neuropathy was low with SG; no inter- accurate assessment. The study did not require real-time
stitial lung disease was reported in the SG arm of this trial. BICR assessment of progressive disease, potentially in-
creasing censoring.
This study has some potential limitations. A number of
patients randomly assigned to the chemotherapy group SG is a Trop-2–directed ADC that demonstrated signifi-
were not treated (n 5 22; 8%), likely because of patient cant clinical benefit and manageable safety compared
preference not to receive standard chemotherapy. Most with standard chemotherapy in a phase III trial of patients
patients had visceral metastases (95%), consistent with with unresectable locally advanced or metastatic heavily
aggressive disease, and had received multiple lines of pretreated, endocrine-resistant HR1/HER2– breast
chemotherapy, which are the factors associated with cancer, a population with limited treatment options. The
shorter PFS and higher neutropenia risk. The heterogeneity magnitude of PFS benefit should be considered in the

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 Rugo et al

TABLE 3. Summary of Treatment-Related AEs of Any Grade ($ 10%) and Worst Grade 2 or Grade $ 3 ($ 5%) in the Safety Population (all patients who
received $ 1 dose of study treatment)
SG (n 5 268) Chemotherapy (n 5 249)

Treatment-Related AEa All Grade Grade 2 Grade ‡ 3 All Grade Grade 2 Grade ‡ 3
Hematologic, No. (%)
Neutropeniab 188 (70) 45 (17) 136 (51) 134 (54) 29 (12) 94 (38)
c
Anemia 91 (34) 44 (16) 17 (6) 62 (25) 31 (12) 8 (3)
Leukopeniad 37 (14) 7 (3) 23 (9) 23 (9) 8 (3) 13 (5)
Lymphopeniae 31 (12) 11 (4) 10 (4) 25 (10) 7 (3) 8 (3)
Febrile neutropenia 14 (5) 0 14 (5) 11 (4) 0 11 (4)
GI, No. (%)
Diarrhea 152 (57) 56 (21) 25 (9) 41 (16) 12 (5) 3 (1)
Nausea 148 (55) 56 (21) 3 (1) 77 (31) 23 (9) 7 (3)
Vomiting 50 (19) 12 (4) 1 (, 1) 30 (12) 8 (3) 4 (2)
Constipation 49 (18) 8 (3) 0 36 (14) 8 (3) 0
Abdominal pain 34 (13) 12 (4) 2 (1) 17 (7) 4 (2) 0
Others, No. (%)
Alopecia 123 (46) 105 (39) 0 41 (16) 18 (7) 0
Fatigue 100 (37) 37 (14) 15 (6) 73 (29) 31 (12) 6 (2)
Asthenia 53 (20) 26 (10) 5 (2) 37 (15) 19 (8) 2 (1)
Decreased appetite 41 (15) 9 (3) 1 (, 1) 34 (14) 13 (5) 1 (, 1)
f
Neuropathy 23 (9) 8 (3) 3 (1) 38 (15) 16 (6) 6 (2)

NOTE. Assessed in the safety population.

Abbreviations: AE, adverse event; SG, sacituzumab govitecan.
a
Patients may report more than one event per preferred term. AEs were coded using Medical Dictionary for Regulatory Activities v24.0, and AE severity was
graded per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.
b
Combined preferred terms of neutropenia and neutrophil count decreased.
c
Combined preferred terms of anemia, hemoglobin decreased, and red blood cell count decreased.
d
Combined preferred terms of leukopenia and WBC count decreased.
e
Combined preferred terms of lymphopenia and lymphocyte count decreased.
f
Combined preferred terms of gait disturbance, hypoesthesia, muscular weakness, neuropathy peripheral, paresthesia, and peripheral sensory neuropathy.

context of the totality of efficacy data from this trial in the treatment including endocrine therapy, a CDK4/6i and at
late-line setting, which all favored SG over chemotherapy, least two lines of chemotherapy (including a taxane) for
with a substantially higher proportion of patients alive and advanced breast cancer.21 Neutropenia and diarrhea are
progression-free at all landmark time points. This novel known AEs with SG and should be prevented and managed
agent directed to a highly expressed target may represent an according to established guidelines.28-32 Additional phase III
important treatment option for these patients, addressing a studies evaluating SG in HR1 breast cancer are underway,
critical unmet medical need. In accordance with the NCCN including GBG102-SASCIA (ClinicalTrials.gov identifier:
Guidelines for Breast Cancer, SG is a preferred therapy NCT04595565)33 and EVER-132-002 (ClinicalTrials.gov
option for patients with HR1/HER22 cancers after prior identifier: NCT04639986).

5
AFFILIATIONS Faculty of Biomedical and Health Sciences, Department of Medicine,
1
Department of Medicine, University of California San Francisco Helen Universidad Europea de Madrid, Madrid, Spain
6
Diller Family Comprehensive Cancer Center, San Francisco, CA Barts Cancer Institute, Queen Mary University of London, London,
2
Medical Oncology, Massachusetts General Hospital Cancer Center, United Kingdom
7
Harvard Medical School, Boston, MA Medical Oncology Department and D3i, Institut Curie, Paris, France
8
3
Medical Faculty Mannheim, Heidelberg University, University Hospital Medical Oncology Department, Centre Léon Bérard, Lyon, France
9
Mannheim, Heidelberg, Germany Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain
10
4
Medical Oncology Department, International Breast Cancer Center, Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France
11
Pangaea Oncology, Quironsalud Group, Madrid and Barcelona, Spain Hospital Universitari Vall D’Hebron, Barcelona, Spain
12
Memorial Sloan-Kettering Cancer Center, New York, NY

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 Sacituzumab Govitecan in HR+/HER2– Metastatic Breast Cancer

13
Department of Clinical Development, Gilead Sciences Inc, Foster City, AUTHOR CONTRIBUTIONS
CA Conception and design: Aditya Bardia, Javier Cortes, Peter Schmid, Sara
14
Department of Global Patient Safety, Gilead Sciences Inc, Foster City, M. Tolaney
CA Provision of study materials or patients: Aditya Bardia, Frederik Marmé,
15
Department of Biostatistics, Gilead Sciences Inc, Foster City, CA Javier Cortes, Delphine Loirat, Eva Ciruelos, Florence Dalenc
16
Department of Medical Oncology, Dana-Farber Cancer Institute, Collection and assembly of data: Hope S. Rugo, Aditya Bardia, Frederik
Boston, MA Marmé, Delphine Loirat, Olivier Trédan, Eva Ciruelos, Patricia Gómez
Pardo, Rosemary Delaney, Sara M. Tolaney
CORRESPONDING AUTHOR Data analysis and interpretation: Hope S. Rugo, Aditya Bardia, Peter
Hope S. Rugo, MD, University of California San Francisco Helen Diller Schmid, Delphine Loirat, Eva Ciruelos, Florence Dalenc, Komal L.
Family Comprehensive Cancer Center, 1825 4th St, San Francisco, CA Jhaveri, Olivia Fu, Lanjia Lin, Wendy Verret, Sara M. Tolaney
94158; e-mail: [email protected]. Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
EQUAL CONTRIBUTION
H.S.R. and A.B. contributed equally to this work.
ACKNOWLEDGMENT
We thank the patients and their caregivers for helping us realize the
SUPPORT possibilities of this research. Thanks to the dedicated clinical trial
Supported by Gilead Sciences Inc. investigators and their devoted team members who participated in this
trial. The study was sponsored by Gilead Sciences Inc and was designed
CLINICAL TRIAL INFORMATION through a collaboration of the sponsor and the lead investigators. The
NCT03901339 and EudraCT 2018-004201-33. authors would also like to thank Jin You, PharmD, and Dustin Chernick,
PhD, of Gilead Sciences for their editorial assistance in preparation of
this manuscript. Medical writing and editorial assistance were provided
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF by Shala Thomas, PhD, CMPP, at Team 9 Science. The TROPiCS-02
INTEREST Study Principal Investigators are listed in Appendix 1 (online only).
Disclosures provided by the authors are available with this article at DOI
https://doi.org/10.1200/JCO.22.01002.

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n n n

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 Sacituzumab Govitecan in HR+/HER2– Metastatic Breast Cancer

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Sacituzumab Govitecan in Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted.
Relationships are self-held unless noted. I 5 Immediate Family Member, Inst 5 My Institution. Relationships may not relate to the subject matter of this manuscript.
For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.
Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Hope S. Rugo Delphine Loirat

Honoraria: Puma Biotechnology, Mylan, Samsung Bioepis, Chugai Pharma, Honoraria: MSD, Gilead Sciences, AstraZeneca, Lilly
Blueprint Medicines, Napo Pharmaceuticals Consulting or Advisory Role: Roche, MSD Oncology, AstraZeneca, Novartis,
Research Funding: OBI Pharma (Inst), Pfizer (Inst), Novartis (Inst), Lilly (Inst), Pfizer, Immunomedics, Gilead Sciences, 4D Pharma, Lilly
Genentech (Inst), Merck (Inst), Odonate Therapeutics (Inst), Daiichi Sankyo Travel, Accommodations, Expenses: Roche, AstraZeneca, MSD, Pfizer, Gilead
(Inst), Sermonix Pharmaceuticals (Inst), AstraZeneca (Inst), Gilead Sciences Sciences
(Inst), Ayala Pharmaceuticals (Inst), Astellas Pharma (Inst), Seattle Genetics
Olivier Trédan
(Inst), MacroGenics (Inst), Boehringer Ingelheim (Inst), Polyphor (Inst)
Consulting or Advisory Role: Roche, Pfizer, Lilly, AstraZeneca, MSD Oncology,
Open Payments Link: https://openpaymentsdata.cms.gov/summary
Daiichi Sankyo Europe GmbH, Eisai Europe, Sandoz-Novartis, Seattle Genetics,
Aditya Bardia Pierre Fabre, Gilead Sciences
Consulting or Advisory Role: Novartis (Inst), Genentech, Pfizer, Spectrum Research Funding: Roche (Inst), Bristol Myers Squibb (Inst), MSD Oncology
Pharmaceuticals, BioTheranostics, Merck, Radius Health (Inst), (Inst), AstraZeneca (Inst), Novartis (Inst), Bayer (Inst),
Immunomedics (Inst), Genentech/Roche (Inst), Pfizer (Inst), Innocrin Pharma Travel, Accommodations, Expenses: Roche, Novartis, Pfizer, Lilly, AstraZeneca,
(Inst), Sanofi, Puma Biotechnology, Daiichi Sankyo/AstraZeneca, Foundation MSD Oncology
Medicine, Philips Healthcare
Eva Ciruelos
Research Funding: Genentech (Inst), Novartis (Inst), Pfizer (Inst), Merck (Inst),
Consulting or Advisory Role: Roche, Pfizer, AstraZeneca, Novartis, Lilly, MSD
Sanofi (Inst), Radius Health (Inst), Immunomedics (Inst), AstraZeneca/Daiichi
Oncology, Daiichi Sankyo/AstraZeneca
Sankyo (Inst)
Speakers’ Bureau: Lilly, Roche, Pfizer, Daiichi Sankyo/AstraZeneca, Novartis
Open Payments Link: https://openpaymentsdata.cms.gov/physician/523675
Travel, Accommodations, Expenses: Roche, Pfizer
Frederik Marmé
Komal L. Jhaveri
Honoraria: Roche/Genentech, Novartis, Pfizer, AstraZeneca, Tesaro, Clovis
Consulting or Advisory Role: Novartis, Pfizer, AstraZeneca, Jounce
Oncology, Eisai, Celgene, Genomic Health, PharmaMar, Amgen, MSD Oncology,
Therapeutics, Synthon, IntelliSphere, Bristol Myers Squibb, Genentech, AbbVie,
Immunomedics (Inst), Settle Genetics, Myriad Genetics, Pierre Fabre,
Lilly, Blueprint Medicines, Seattle Genetics, Daiichi Sankyo, Biotheranostics,
GlaxoSmithKline, AGENDIA, Lilly, Gilead Sciences
Sun Pharma Advanced Research Company, Taiho Oncology, Sanofi, Gilead
Consulting or Advisory Role: AstraZeneca (Inst), Tesaro, Pfizer, Roche (Inst),
Sciences
Genomic Health, CureVac, Amgen, Vaccibody (Inst), Immunomedics (Inst),
Research Funding: Novartis (Inst), Genentech (Inst), Debiopharm Group (Inst),
Eisai, GlaxoSmithKline, Gilead Sciences
ADC Therapeutics (Inst), Pfizer (Inst), Novita Pharmaceuticals (Inst), Clovis
Research Funding: Roche/Genentech (Inst), Novartis (Inst), AstraZeneca (Inst),
Oncology (Inst), Lilly (Inst), Zymeworks (Inst), Immunomedics (Inst), Puma
Tesaro (Inst), Clovis Oncology (Inst), MSD Oncology (Inst), Vaccibody (Inst),
Biotechnology (Inst), VelosBio/Merck (Inst), AstraZeneca (Inst)
Gilead Sciences (Inst), GlaxoSmithKline (Inst)
Travel, Accommodations, Expenses: Taiho Pharmaceutical, Jounce
Travel, Accommodations, Expenses: Roche, Pfizer, AstraZeneca
Therapeutics, Pfizer, AstraZeneca, IntelliSphere, Lilly, Gilead Sciences
Javier Cortes
Rosemary Delaney
Stock and Other Ownership Interests: MedSIR, Nektar, Leuko (I)
Employment: Gilead Sciences
Honoraria: Novartis, Eisai, Celgene, Pfizer, Roche, Samsung, Lilly, Merck Sharp
Stock and Other Ownership Interests: Immunomedics (I), Gilead Sciences
& Dohme, Daiichi Sankyo
Consulting or Advisory Role: Celgene, Cellestia Biotech, AstraZeneca, Roche, Olivia Fu
Settle Genetics, Daiichi Sankyo, ERYTECH Pharma, Polyphor, Athenex, Lilly, Employment: Gilead Sciences
Servier, Merck Sharp & Dohme, GlaxoSmithKline, Leuko, Clovis Oncology, Stock and Other Ownership Interests: Gilead Sciences
Bioasis, Boehringer Ingelheim, Ellipses Pharma, HiberCell, BioInvent, GEMoaB, Travel, Accommodations, Expenses: Gilead Sciences
Gilead Sciences, Menarini, Zymeworks, Reveal Genomics
Lanjia Lin
Research Funding: ARIAD (Inst), AstraZeneca (Inst), Baxalta (Inst), Bayer (Inst), Employment: Gilead Sciences
Eisai (Inst), Guardant Health (Inst), Merck Sharp & Dohme (Inst), Pfizer (Inst),
Stock and Other Ownership Interests: Gilead Sciences
Puma Biotechnology (Inst), Queen Mary University of London (Inst), Roche
Travel, Accommodations, Expenses: Gilead Sciences
(Inst), Piqur (Inst)
Patents, Royalties, Other Intellectual Property: Pharmaceuticals Combinations Wendy Verret
of A Pi3k Inhibitor and a Microtubule Destabilizing Agent. Javier Cortes Castan, Employment: Roche/Genentech, Gilead Sciences
Alejandro Piris Gimenez, Violeta Srra Elizalde. WO 2014/199294 A, Her2 as a Sara M. Tolaney
predictor of response to dual HER2 blockade in the absence of cytotoxic therapy, This author is a member of the Journal of Clinical Oncology Editorial Board.
Aleix Prat, Antonio Llombart, Javier Cortes, US 2019/0338368 A1 Journal policy recused the author from having any role in the peer review of this
Travel, Accommodations, Expenses: Roche, Pfizer, Eisai, Novartis, Daiichi manuscript.
Sankyo, Gilead Sciences Consulting or Advisory Role: Novartis, Pfizer, Merck, Lilly, Nektar, NanoString
Peter Schmid Technologies, AstraZeneca, Puma Biotechnology, Genentech, Eisai, Sanofi,
Employment: Roche (I) Bristol Myers Squibb, Paxman, Seattle Genetics, Odonate Therapeutics, G1
Honoraria: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Therapeutics, OncoPep, Kyowa Hakko Kirin, Samsung Bioepis, CytomX
Puma Biotechnology, Roche, Eisai, Celgene Therapeutics, Daiichi Sankyo, Athenex, Immunomedics/Gilead, Mersana,
Consulting or Advisory Role: Genentech/Roche (I), AstraZeneca, Merck, Certara Inc, 4D Pharma, Ellipses Pharma, OncoSec, Chugai Pharma,
Boehringer Ingelheim, Bayer, Pfizer, Novartis, Eisai, Celgene, Puma BeyondSpring Pharmaceuticals, OncXerna Therapeutics, Infinity
Biotechnology Pharmaceuticals, Zymeworks, Zentalis, BluePrint Medicines, Reveal Genomics
Research Funding: AstraZeneca (Inst), Astellas Pharma (Inst), OncoGenex Research Funding: Genentech/Roche (Inst), Merck (Inst), Exelixis (Inst), Pfizer
(Inst), Genetech (Inst), Novartis (Inst), Roche (Inst), Medivation (Inst), Lilly (Inst), Novartis (Inst), Bristol Myers Squibb (Inst), Eisai (Inst),
AstraZeneca (Inst), NanoString Technologies (Inst), Cyclacel (Inst), Nektar
(Inst), Immunomedics (Inst), Odonate Therapeutics (Inst), Sanofi (Inst), Settle
Genetics (Inst)
No other potential conflicts of interest were reported.

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 Rugo et al

APPENDIX 1. LIST OF TROPICS-02 STUDY PRINCIPAL

INVESTIGATORS

Study Investigator Study Institution

Maysa Abu-Khalaf Thomas Jefferson University
Foluso Ademuyiwa Washington University School of Medicine
Clarence Adoo HonorHealth Research Institute
Philippe Aftimos Institut Jules Bordet
Samreen Ahmed University Hospitals of Leicester NHS Trust
Cristina Alencar Virginia Oncology Associates
Anne Armstrong The Christie NHS Foundation Trust
Cristina Arqueros Hospital de la Santa Creu i de Sant Pau
Jean-Pierre Ayoub Centre Hospitalier De l’Universite De Montreal CHUM
Aditya Bardiaa Massachusetts General Hospital
J. Thaddeus Beck Highlands Oncology Group
Giampaolo Bianchini Ospedale San Raffaele
Sibel Blau Northwest Medical Specialties, PLLC
Nathalie Bonnin Hospices Civils de Lyon
Adam Brufsky UPMC Hillman Cancer Center
Christina Brzezniak Virginia Cancer Specialists, PC
Giuseppe Cairo Ospedale Vito Fazzi di Lecce
Lourdes Calvo Martinez Complejo Hospitalario Universitario A Coruña
Luigi Cavanna Azienda Unità Sanitaria Locale di Piacenza-Ospedale
Guglielmo da Saliceto
Marina Elena Azienda Ospedaliera San Gerardo di Monza
Cazzaniga
Eva Ciruelos Hospital Universitario 12 de Octubre
Patrick Cobb Saint Vincent Frontier Cancer Center
Javier Cortes Castana Hospital Ruber Internacional
Ricardo Costa Moffitt Cancer Center
Florence Dalenc Institut Claudius Regaud
Maaike de Boer Maastricht University Medical Center
Neelam Desai Beth Israel Deaconess Medical Center
Jennifer Diamond University of Colorado
Erion Dobi Hôpital Jean Minjoz
Lara Durna Kaiser Permanente Medical Center
Peter Fasching Universitätsklinik Erlangen
Gianluigi Ferretti Istituto Regina Elena
Nelly Firmin Institut Regional du Cancer de Montpellier
Keerthi Gogineni Emory University
Patricia Gomez Pardo Hospital Universitari Vall D’Hebron
Julien Grenier Institut Sainte Catherine
Erika Hamilton Tennessee Oncology
Susanna Onkologische Schwerpunktpraxis Eppendorf
Hegewisch-Becker
(continued on following page)

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 Sacituzumab Govitecan in HR+/HER2– Metastatic Breast Cancer

(continued)
Study Investigator Study Institution
Stephanie Henry CHU UCL NAMUR—Sainte Elisabeth
Dawn Hershman Columbia University Medical Center
Claudine Isaacs Georgetown University
Jean-Philippe Jacquin Institut de Cancerologie Lucien Neuwirth
Komal Jhaveri Memorial Sloan-Kettering Cancer Center
Virginia Kaklamani University of Texas Health Science Center at San
Antonio
Hans-Christian Kolberg Marienhospital Bottrop
Amy Krie Virginia Piper Cancer Center (Alliant Health)
Christian Kurbacher Gynakologisches Zentrum Bonn
Charles Kurkul Texas Oncology PA
Sylvain Ladoire Centre Georges François Leclerc
Sabine Linn Antoni van Leeuwenhoekziekenhuis
Delphine Loirat Institut Curie
Rafael Lopez Hospital Clı́nico Universitario de Santiago de
Compostela—CHUS
Kristina Lübbe DIAKOVERE Krankenhaus gGmbH Henriettenstift—
Standort Kirchrode
Hans-Joachim Luck Gynakologisch-Onkologische Praxis Hannover
Elisabeth Luporsi Hôpital de Mercy
Ling Ma Rocky Mountain Cancer Center
Rolf Mahlberg Klinikum Mutterhaus der Borromaerinnen
Frederik Marmea Universitatsmedizin Mannheim
Miguel Martin Jimenez Hospital General Universitario Gregorio Marañón
Eduardo Martinez Hospital Provincial de Castellón
Ingrid Mayer Vanderbilt University
Kelly McCann University of California Los Angeles (UCLA)
Serafı́n Morales Hospital Universitari Arnau De Vilanova (Huav)
Sarah Mougalian Yale University
Rita Nanda University of Chicago
Polly Niravath Houston Methodist Hospital
Yelena Novik New York University School of Medicine
Shannon O’Connor Maryland Oncology Hematology
Alicia Okines The Royal Marsden NHS Foundation Trust
Coral Omene Rutgers Cancer Institute of New Jersey
Rianne Oosterkamp Medisch Centrum Haaglanden Antoniushove
Joyce O’Shaughnessy Texas Oncology
Steven Papish Summit Medical Group
Ritesh Parajuli University of California Irvine (UCIMC)
Felicity Paterson Royal Surrey County Hospital NHS Foundation Trust
Michel Pavic Centre Hospitalier De I’Universite De Sherbrooke
Hôpital Fleurimont
Rebecca Pedersini Azienda Ospedaliera Spedali Civili di Brescia
Alejandra Perez Sylvester Comprehensive Cancer Center
Timothy Pluard St Luke’s Cancer Institute
(continued on following page)

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 Rugo et al

(continued)
Study Investigator Study Institution
David Potter Masonic Cancer Center
Paola Pozzi Ospedale di Desio
Kevin Punie Universitaire Ziekenhuis Leuven
Fabricio Racca Hospital Quironsalud Barcelona
Daniel Rayson Queen Elizabeth II Health Sciences Center
Mattea Reinisch Kliniken Essen-Mitte
Paul Richards Blue Ridge Cancer Care
Elizabeth Riley James Graham Brown Cancer Center
David Riseberg Mercy Medical Center
Regan Rostorfer University of Florida
Hope Rugoa University of California San Francisco
Manuel Ruiz Borrego Hospital Universitario Virgen del Rocio
Sagar Sardesai Stefanie Spielman Comprehensive Breast Center
a
Peter Schmid Barts Health NHS Trust
Andreas Schneeweiss Nationales Centrum für Tumorerkrankungen
Heidelberg
Holger Schultz HELIOS Klinikum Berlin-Buch
Lee Schwartzberg West Clinic
Lasika Seneviratne Los Angeles Hematology Oncology Medical Group
Priyanka Sharma University of Kansas
Sasha Strain Texas Oncology PA
Rachel Swart Arizona Oncology Associates
Karen Tedesco New York Oncology Hematology—Amsterdam Cancer
Center
Hans Tesch Centrum für Hämatologie und Onkologie Bethanien
Amy Tiersten Mount Sinai
Sara Tolaneya Dana Farber Cancer Institute
Olivier Trédan Centre Leon Berard
Nisha Unni University of Texas Southwestern Medical Center
Thierry Velu Chirec Cancer Institute
Hermann Voss Stadtisches Klinikum Dessau
Grace Wang Baptist Health—Miami Cancer Institute
Rudolf Weide Praxisklinik für Hämatologie und Onkologie Koblenz
Duncan Wheatley Royal Cornwall Hospital Trust
Kay Yeung University of California San Diego
Amelia Zelnak Northside Hospital Atlanta
a
Denotes members of the TROPiCS-02 scientific steering committee.

© 2022 by American Society of Clinical Oncology

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