Abstract 42P
Background
After 4 y of follow-up in patients (pts) enrolled in China in the phase III KEYNOTE-042 study, pembrolizumab (pembro) improved OS vs chemotherapy (chemo) in pts with previously untreated advanced or metastatic NSCLC without EGFR/ALK alterations in the PD-L1 tumor proportion score (TPS) ≥50% (HR, 0.66; 95% CI, 0.45–0.95), ≥20% (0.68, 0.49–0.93), and ≥1% (0.67, 0.51–0.89) groups. We report results after 16 mo of additional follow-up.
Methods
Eligible pts were randomized 1:1 to receive pembro 200 mg Q3W for ≤35 cycles or carboplatin + paclitaxel or pemetrexed with optional pemetrexed maintenance (nonsquamous only). Primary endpoints were OS in pts with PD-L1 TPS ≥50%, ≥20%, and ≥1%. No alpha was assigned to this exploratory analysis of pts enrolled in China in KEYNOTE-042 global (NCT02220894) and China extension (NCT03850444) studies.
Results
Of 262 pts enrolled in China, 128 were randomized to pembro and 134 to chemo. Median time from randomization to database cutoff (Sep 12, 2022) was 63.7 (range, 56.3–72.6) mo. Pembro prolonged OS vs chemo in pts with PD-L1 TPS ≥50% (HR 0.65, 95% CI 0.45–0.93), ≥20% (0.67, 0.49–0.91), and ≥1% (0.66, 0.51–0.87). 5-y OS rates were ∼2 fold higher with pembro vs chemo across all 3 PD-L1 TPS groups (table). Grade 3–5 treatment-related AEs occurred in 19.5% of pts in the pembro arm and 68.8% in the chemo arm. Of 22 pts who completed 35 cycles of pembro, ORR was 81.8% (95% CI, 59.7%–94.8%) and 3-y OS rate after completion of 35 cycles (∼5 y after randomization) was 56.6%. At data cutoff, 80 pts in the pembro arm and 79 in the chemo arm had begun subsequent therapy; 5 pts began second-course pembro.
Table: 42P| PD-L1 TPS ≥50% | PD-L1 TPS ≥20% | PD-L1 TPS ≥1% | ||||
|---|---|---|---|---|---|---|
| Pembro n = 72 | Chemo n = 74 | Pembro n = 101 | Chemo n = 103 | Pembro n = 128 | Chemo n = 134 | |
| OS, median (95% CI), mo | 24.5 (17.4–34.3) | 13.8 (10.1–18.3) | 21.9 (17.4–27.0) | 13.5 (10.1–17.9) | 20.2 (17.4–25.3) | 13.5 (10.1–17.9) |
| OS HR (95% CI) | 0.65 (0.45–0.93) | 0.67 (0.49–0.91) | 0.66 (0.51–0.87) | |||
| 5-y OS rate (95% CI), % | 18.4 (10.2–28.5) | 8.3 (3.3–16.2) | 19.1 (12.0–27.5) | 10.2 (5.2–17.1) | 19.0 (12.6–26.4) | 9.5 (5.2–15.5) |
| ORR (95% CI), % | 41.7 (30.2–53.9) | 24.3 (15.1–35.7) | 34.7 (25.5–44.8) | 24.3 (16.4–33.7) | 32.0 (24.1–40.9) | 24.6 (17.6–32.8) |
| DOR, median (range), mo | 16.5 (1.4+ to 64.1+) | 11.7 (1.6+ to 63.4+) | 16.5 (1.4+ to 64.1+) | 10.9 (1.6+ to 63.4+) | 16.0 (1.4+ to 64.1+) | 10.9 (1.1+ to 63.4+) |
Conclusions
Similar to the global KEYNOTE-042 study, after 5 y of follow-up, pembro continued to demonstrate improved OS vs chemo with manageable safety in Chinese pts with previously untreated advanced or metastatic NSCLC without EGFR/ALK alterations with PD-L1 TPS ≥1%. These data further support pembro monotherapy as a standard of care for these pts.
Clinical trial identification
NCT02220894 and NCT03850444.
Editorial acknowledgement
Writing support was provided by Kathleen Estes, PhD, of ICON plc (Blue Bell, PA, USA), funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Funding
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Disclosure
Y. Wu: Financial Interests, Personal, Research Grant: AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Novartis, Takeda, MSD; Financial Interests, Personal, Other, Honorarium: AstraZeneca, BeiGene, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sanofi (all not promotional activities). L. Zhang: Financial Interests, Personal, Research Grant: Hengrui, BMS, and Innovent Biologics. Q. Zhou: Financial Interests, Personal, Other, Lecture and presentations fees to myself: AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, and Sanofi outside the submitted work. C. Zhou: Financial Interests, Personal, Other, honoraria: Boehringer Ingelheim, Eli Lilly, Hengrui, MSD, Sanofi, F. Hoffmann-La Roche Ltd., and Qilu. C.G. Arenas: Financial Interests, Personal, Full or part-time Employment: MSD Spain; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA. Z. Chen: Financial Interests, Personal, Full or part-time Employment: MSD China. W.C. Yu: Financial Interests, Personal, Full or part-time Employment: MSD China. T.S.K. Mok: Financial Interests, Personal, Research Grant: AstraZeneca, Bristol Myers Squibb, Clovis Oncology, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, and XCovery; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Bristol Myers Squibb, Taiho, and Takeda Oncology; Financial Interests, Personal, Other, honoraria: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, SFJ Pharmaceuticals, ACEA Biosciences, Inc., Vertex Pharmaceuticals, Bristol Myers Squibb, OncoGe; Financial Interests, Personal, Stocks/Shares: Sanomics Ltd.; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Clovis Oncology, Merck Serono, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, SFJ Pharmaceuticals, ACEA Biosciences, Inc., Vertex Pharmaceutical. All other authors have declared no conflicts of interest.