ESMO Direct Verbal Report Phase III Study: How to Choose Adjuvant Therapy for Resectable NSCLC?

Editor: Xiaoyuan

Medical pulse through the collation, unauthorized please do not reprint
.

The European Society for Internal Oncology (ESMO) Annual Meeting is the most prestigious and influential oncology conference
in Europe.

This paper collates the results
of two key Phase III research advances in the field of perioperative NSCLC treatment in the oral presentation.

Phase III KEYNOTE-091 study subgroup analysis

Professor Solange Peters

background

Patients with complete resection of stage IB (T 4cm) to IIIA NSCLC (AJCC v7) can receive ≤ 4 cycles of adjuvant chemotherapy
according to the PEARLS/KEYNOTE-091 study as recommended by local guidelines.

method

Eligible patients are randomly assigned to receive pabolivizumab (200 mg, Q3W) and placebo (18 doses) in a 1:1 ratio
.

Study the design

outcome

Among the 1177 patients who received the randomized grouping, 39.
5%, 32.
2%, and 28.
3% of the patients had PD-L1 TPS<1%, 1-49%, ≥50%,
respectively.
In the ITT population and TPS ≥ 50% of the population, the baseline characteristics of the pabolizumab group and the placebo group were balanced and comparable
.
In the total population, compared with the placebo group, pabolizumab resulted in a significant improvement in DFS in the total population, but not significantly in the PD-L1 TPS ≥ DFS in
50% of the population.
OS data is immature
.

Primary endpoint

The general population and PD-L1 TPS ≥ characteristic of 50% of patients

In the Pabolivizumab and placebo groups, the incidence of grade 3-5 adverse events (AEs) was 34.
1% vs 25.
8% (ITT), 37.
8% vs 25.
0% (TPS≥50%), and AE resulted in discontinuation of the drug
in 19.
8% vs 5.
9% (ITT) and 23.
2% vs 6.
7% (TPS≥50%), respectively 。 Compared with the placebo group, pabolivizumab improved DFS in the PD-L1 TPS ≥ 50% (HR=0.
82), PD-L1 TPS 1-49% (HR=0.
67), and PD-L1 TPS <1% (HR=0.
78) subgroups
.

DFS in each subgroup of patients

The DFS had different levels of PD-L1 TPS in the two groups

conclusion

As expected, in the Pabolizumab group, the median DFS and long-term DFS in the TPS < 50% subgroup were numerically superior
compared to the TPS 1-49% and ≥1% subgroups.
Unexpectedly, the same trend
was observed in the placebo group.

In the next interim analysis, DFS will be further published ≥ 50% of patients with DFS
.
Overall, the findings support the use of pabolivizumab for complete resection of adjuvant therapy in patients with stage IB-IIIA NSCLC (before adjuvant chemotherapy),
regardless of PD-L1 expression.

Phase III JIPANG study OS final analysis

Professor Kiyotaka Yoh

background

The JIPANG study showed that Pemetrexed/cisplatin(Pem/Cis) and vinorebin/cisplatins (Vnr/Cis) showed similar recurrence-free survival (RFS) and were better tolerated as adjunctive chemotherapy after surgery in patients with complete resection non-squamous NSCLC
.
One of the secondary endpoints of the study was overall survival (OS
).
At this year's ESMO conference, Professor Kiyotaka Yoh announced the final analysis of
the Phase III JIPANG study OS.

method

Patients with complete resection of stage II-IIIA non-squamous NSCLC were randomly assigned to receive pemetrexed (500 mg/m2, day 1)/cisplatin (75 mg/m2, day 1) or vinoreribin (25 mg/m2, days 1 and 8)/cisplatin (80 mg/m2, day 1)
in a 1:1 ratio.
Stratified factors include sex, age, pathological stage, EGFR mutation status, and research centers
.
In this analysis, the researchers analyzed data from the last patient 5 years after enrollment
.

Study the design

outcome

Between March 2012 and August 2016, a total of 804 patients were randomized
.
A total of 783 patients were analyzed, and there were 389 patients in the pemetrexed/cisplatin group and vinoresplatin/cisplatin group, respectively, with a median age of 65 years, 52% and 52% of patients with stage IIIA, and 24% and 25%
of patients with EGFR mutation, respectively.

Patient baseline features

The updated results showed that the median RFS in the pemetrexed/cisplatin group and the vincispin group, respectively (HR=0.
95, P=0.
249), and the median follow-up was 77.
3 months, and the 3-year and 5-year OS rates of the pemetrexed/cisplatin and vinzeplatin/cisplatin groups were 87.
0% vs 84.
1% vs 84.
1% and 75.
6% (HR=1.
04, P=0.
598),
respectively.

RFS and OS 5 year follow-up results

In the OS subgroup analysis, the HR of patients with EGFR mutation and no EGFR mutation was 1.
93 (95% CI, 1.
13 to 3.
28) and 0.
86 (95% CI, 0.
64 to 1.
14) (P=0.
011),
respectively.

OS subgroup analysis

In a total of 441 patients with relapses observed, brain metastases occurred in 30.
3% (pemetrexed/cisplatin) and 18.
6% (vincisplatin/cisplatin
) in the EGFR mutation subgroup, respectively.
In the subgroup without EGFR mutation, brain metastases occurred in 18.
6% (pemetrexed/cisplatin
) and 27.
5% (vinpolidin/cisplatin group), respectively.

Common recurrence sections and analysis

conclusion

The final analysis of the study showed that pemetrexed/cisplatin and vinoresplatin/cisplatin showed similar benefits
in the complete resection of RFS and OS in patients with stage II-IIIA non-squamous NSCLC.
To date, pemetrexed/cisplatin/cisplatin/cisplatin adjuvant therapy shows the longest OS
compared to historical data.
Regardless of the EGFR mutation status, brain metastases
occur in 20-30% of patients after two adjuvant chemotherapy.

References:

930MO-PD-L1 expression and outcomes of pembrolizumab and placebo in completely resected stage IB-IIIA NSCLC: Subgroup analysis of PEARLS/KEYNOTE-091.
2022 ESMO.

931MO-Final overall survival analysis of phase III study of pemetrexed/cisplatin versus vinorelbine/cisplatin for completely resected non-squamous non-small cell lung cancer: The JIPANG Study.
2022 ESMO.