JOURNAL CLUB-TPF VS TP in NACT oral cancer..pptx

JOURNAL CLUB
TPF v/s TP in NACT oral cancer
Dr Maroti
(HNSOG Fellow)
1

2
Definition
● Neoadjuvant therapy refers to any treatment that is given for
cancer before the main treatment, with the goal of making the main
treatment more likely to be successful.

WHAT IS THE ROLE OF NACT IN ORAL CANCER
● TO DOWNSIZE THE TUMOR
● ORGAN PRESERVATION
3

4
Lacitra et al
2003
RESECTABLE
OSCC
TECHNICALLY UNRESECTABLE/
BORDERLINE RESECTABLE
Zhong et al
2014
Chaukar et al
2021
UNRESECTABLE
there was a trend toward a lower incidence of distant
metastasis (5.5% vs. 8.7%);
In the NACT arm, patients who had a complete
pathological response had an improved survival as
compared to those with an unfavorable response or
those in the non-NACT group.
there was increased mandibular preservation seen
in the study by Licitra et al. as well as a lesser need
of adjuvant RT.

The definition of resectability in oral cancers is subjective. Resectability
depends upon
the extent of disease, invasion,
attainability of clear margins, and
ability to perform a functional
resection and reconstruction, thus minimizing the loss of function
5

6
‘Technically unresectable’

What are the available options in such cases?
7
CTRT
dismal outcomes
NACT—-->SURG
UPFRONT SURG
High morbidity

Commonly regimen is chosen based on the
patient’s performance status, creatinine clearance, financial constraints, and
patient preference
8
2 drugs
regimen
3 drugs
regimen

- The 2-drug regimen of docetaxel-platinum (TP) has shown promising
results in multiple studies in locally advanced head and neck SCC. T
- his regimen is preferred in community practice due to the logistic
difficulty of the requirement for inpatient admission for continuous
infusion of 5FU and its associated side effect profile including not
insignificant treatment-related mortality.
However, never been compared in a prospective randomized study to TPF
9

11
Methods
phase 3,
randomized,
parallel-arm,
open label,
Superiority design,
and single-center study.

Participants
Patients with borderline resectable oral cancer as per the below mentioned criteria (meeting
minimum one)
1. Buccal mucosa primary, with diffuse margins and peritumoral soft tissue going up to or above
the level of the zygomatic arch and without any satellite nodules.
2. Tongue primary (anterior two-thirds) with the tumor extending up to or below the level of the
hyoid bone.
3. Extension of tumor of the anterior two-thirds of the tongue to the vallecula,
4. Extension of primary into the high infratemporal fossa
5. Extensive skin infiltration impacting the achievement of negative Margins.
6. Disease encasing the carotid 180 degrees-270 degrees. 12

Block-stratified randomization
Stratification for platinum was done (carboplatin and cisplatin).
13

➔ TPF regimen was administered inpatient and consisted of docetaxel at a dose of 75 mg/m 2 ,
administered as a 1-hour infusion on day 1, followed by cisplatin at a dose of 75 mg/m 2 ,
administered as a 1-hour infusion on day 1, and 5-FU at a dose of 750 mg/m 2 per day,
administered as a continuous infusion on days 1 to 5.
➔ The TP regimen consisted of cisplatin at a dose of 75 mg/m 2 , administered as a 1-hour
infusion on day 1, and docetaxel at a dose of 75 mg/m 2 , administered as a 1-hour infusion on
day 1.
If cisplatin was replaced by carboplatin, then a dose of AUC-5 was used and administered as a 1-
hour infusion on day 1.
administered every three weeks (defined as one cycle) for two cycles
14

➔ Treatment was stopped if there was progressive disease.
➔ evaluated after two cycles of chemotherapy with axial imaging (in accordance
with [RECIST] version 1.1
➔ Based on the response and performance status, further treatment, either
surgery (within 3–8 weeks) followed by adjuvant or radical chemoradiation or
palliative therapy was planned.
➔ Adjuvant chemoradiation was offered to all patients, irrespective of
postoperative histopathology 15

primary endpoint was overall survival (OS) and secondary endpoints were
progression-free survival (PFS) and adverse events.
16

Sample size
The percentage surviving at 12 months in the TP arm was assumed to
be 42% and we expected this to increase to 55% in the TPF arm. With
an alpha of 0.05 and a power of 80%, required 492 patients for this
study.
17

20
Variable Docetaxel +
platinum (TP) arm
(n=248)- Number
(%)
Docetaxel +
platinum + 5-
fluorouracil (TPF)
arm (n=247)-
Number (%)
P-Value
Peritumoral edema
of the disease up to
zygomatic arch
126 (50.8) 107 (43.3) 0.105
Disease close to
hyoid or vallecula*
88 (35.5) 116 (47) 0.011
Extension of disease
into high
infratemporal fossa
48 (19.4) 35 (14.2) 0.149
Extensive skin
infiltration
31 (12.5) 28 (11.3) 0.782
Encasement of 7 (2.8) 6 (2.4) 1

reasons for receiving less than two cycles
21
Variable Docetaxel + platinum
(TP) arm (n=248) –
Number (%)
Docetaxel + platinum + 5-
fluorouracil (TPF) arm
(n=247) – Number (%)
Not applicable 227 (91.5) 217 (87.9)
Never started 5 (2.0) 11 (4.5)
Adverse event 6 (2.5) 8 (3.2)
Progression 8 (3.2) 6 (2.4)
Deterioration in
performance status
- 1 (0.4)
Patient’s preference 2 (0.8) 4 (1.6)

Outcomes
● median follow-up was 45.3 months
● Overall, 199 events of death occurred in the TP arm and 183 in the TPF arm.
● The median OS was 10.3 months (95% CI 8.6–11.5) and 12.0 months (95% CI
10.6- 14.4) in the TP and TPF arms, respectively (P=0.014).
22

The 5-year OS was 18.5% (95% CI 13.8–
23.7) and 23.9% (95% CI 18.1–30.1) in TP
and TPF arms, respectively
23

The median PFS was 5.5 months
(95% CI 4.7–6.4) and 8.1 months (95%
CI 6.7–9.8) in the TP and TPF arms,
respectively (P=0.006)
5-year PFS was
15.4% (95% CI 10.1–21.7) and 22.5%
(95% CI 17.3–28.0) in TP and TPF
24

26
Variable Hazard ratio 95% confidence interval of
hazard ratio
P value
Age
60 years and over Reference
< 60 years 0.904 0.594-1.374 0.636
Eastern Cooperative Oncology Group Performance status
0 Reference
1-2 1.516 1.186-1.939 0.001
Tumor site
Others Reference
Buccal mucosa 1.240 0.861-1.786 0.247
Tongue 0.912 0.639-1.302 0.612
Stage grouping
IVA Reference
IVB 1.116 0.655-1.904 0.686

27
T Grouping
T4a Reference
T4b 1.075 0.629-1.836 0.792
Platinum received
No platinum Reference
Carboplatin 1.877 1.078-3.269 0.026
Cisplatin 1.347 0.920-1.973 0.126
Arm
Docetaxel + platinum (TP) Reference
fluorouracil (TPF)
0.769 0.626-0.943 0.012

sites of the first progression
28
Variable Docetaxel + platinum
(TP) arm (n=248)-
Number (%)
fluorouracil (TPF) arm
(n=247)- Number (%)
Local 179 (72.2) 173 (70)
Regional 117 (47.2) 118 (47.8)
Distant 16 (6.5) 19 (7.7)

Post neoadjuvant treatment
The response rates in the
TPF and TP arms were
28.4% (69; n =243) and
32.6% (77; n =236),
respectively (P=0.323)
30
platinum (TP) arm
(n=243*) – Number
(%)
Docetaxel +
platinum + 5-
fluorouracil (TPF)
arm (n=236*) –
Number (%)
P-Value
Surgery 84 (34.6) 87 (36.8) 0.634
Definitive
Chemoradiation
24 (9.9) 29 (12.3) 0.467
Palliative radiation 27 (11.1) 28 (11.9) 0.886
Palliative
chemotherapy
92 (37.8) 75 (31.8) 0.180
Best supportive Care 16 (6.6) 17 (7.2) 0.858

Surgery
surgery performed was in accordance with the post-NACT tumor volumes
Post NACT, the disease was deemed to be resectable in 217 (43.8%), but 171
(34.5%) underwent surgery; 84 in the TP and 87 in the TPF arm (P=0.634).
median time from commencement of chemotherapy to surgery was 73.5
days and 85 days in TP and TPF arms, respectively.
31

Adjuvant tt details
33
platinum (TP) arm
(n=84)- Number (%)
Docetaxel +
platinum + 5-
fluorouracil (TPF)
arm(n=87)-
Number (%)
Total (n=171)
Adjuvant
chemoradiation
78 (92.9) 79 (90.8) 157 (91.8)
Adjuvant radiation 2 (2.4) 2 (2.3) 4 (2.3)
No adjuvant
therapy
4 (4.8) 6 (6.8) 10 (5.9)
Reasons for no
adjuvant therapy
Was not offered
Patient’s preference
Progression before
starting adjuvant
3 (3.6)
1 (1.2)
-
2 (2.3)
3 (3.4)
1 (1.1)
5 (2.9)
4 (2.4)
1 (0.6)

overall survival- patients who became
resectable post NACT) whether opted for
surgery or not
The 5-year OS in the patients whose
disease had become resectable and
underwent resection versus those
who refused surgery were 50.7%
(95%CI 41.5–59.1) and 12.4% (4.5–
24.6), respectively
34

overall survival- patients who underwent surgery according to the arm of therapy
The 5-year OS in patients who
underwent surgery in the TP and
the TPF arms was 47.2% (95% CI
35.9–57.7) and 55.2% (95% CI 41.9–
66.7), respectively (P = 0.22)
35

OS - who had pathological complete response versus those who did not
5-year OS in patients who
had pathological complete
response versus those who
did not was 90.7% (95% CI
67.6–97.6) and 43.6% (32.4–
54.3), respectively (P = 0.0004)
36

Definitive chemoradiation
median OS in the TP and TPF
arms were 8.6 (95%CI 5.9–
11.2) and 14.4 (95%CI 10.6–
23.5) months, respectively (P
= 0.0036).
The 5-year OS overall was 0%
and 11.2% (95% CI 2.9–26) in
the TP and the TPF arms,
respectively
37

Palliative therapies
The median OS in the TP
and TPF arms were 7.5
(95% CI 6.4–7.9) and 8.0
(95% CI 7.4–9.3) months,
respectively
38

Discussion
❏ NACT followed by assessment for surgery is the standard approach in
these borderline resectable oral cancers
❏ the TPF regimen resulted in a 5.4% absolute improvement in OS and a
23.8% proportional increment in OS over TP.
❏ Although the adverse events with TPF were higher than with TP, they
were manageable and there was much lower mortality
❏ resectability rate (i.e., the proportion of patients deemed to have
resectable disease post-NACT) was 43.8%
39

overall response to NACT in our study was around 33%. This is lower than
what has been reported in head and neck squamous cell carcinoma
-Oral cavity cancers and higher-stage tumors have a lower response than
lower-stage tumors (responses were observed in 63%, 27%, and 18% of stage
II, III, and IV tumors respectively)
40

limitations and strengths
● single tertiary care academic center
● imbalances in age and stage grouping
(more Stage IVb patients in the TP arm,
more patients aged 60 years or over in the
TPF arm)
● indication for NACT (more patients with a
functional indication in the TPF arm)
● differences in therapy (more patients who
received carboplatin in the TP arm, and
more patients who continued
chemotherapy beyond two cycles in the TPF
arm)
41
● represents a real-world scenario where
the majority of patients in the Indian
subcontinent
● homogeneous group of nearly 500
patients

Conclusion
➔ TPF chemotherapy regimen as NACT improves PFS and OS in comparison
to the TP regimen in borderline resectable oral cancers
42

● 721 patients
● 43%) had sufficient reduction in tumour size and underwent surgical
resection
● LRC- 32% in patients undergoing surgery and 15% in patients
undergoing non surgical treatment (p=0.0001)
● The median estimated OS in patients undergoing surgery was 19.6
months (95% CI, 9.59-25.21 months) and 8.16 months (95%, CI 7.57-8.76)
in patients treated with non surgical treatment (p=0.0001).
43

● unsuitable for TPF were selected
● received 2 drug regimen of intravenous PC with 3 drug regimen of weekly
methotrexate 9 mg per m2, Celecoxib 200 mg twice daily, erlotinib 150 mg
once daily all administered orally
● 72 patients
● response rate was 61.1% and grade 3 and above adverse event rate was
33.5%.
● overall estimated PFS and OS were 18.5 (95%CI = 14.4-22.7) months and
18.05 (95%CI = 14.2-21.8) months respectively 44

JOURNAL CLUB-TPF VS TP in NACT oral cancer..pptx

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JOURNAL CLUB-TPF VS TP in NACT oral cancer..pptx