Carboplatin-paclitaxel/nab-paclitaxel with or without pembrolizumab in first-line metastatic squamous NSCLC: results from the KEYNOTE-407 East Asia...

Date 25 November 2018
Event ESMO Asia 2018 Congress
Session Mini Oral - Thoracic cancers
Topics Immunotherapy
Presenter Terufumi Kato
Citation Annals of Oncology (2018) 29 (suppl_9): ix150-ix169. 10.1093/annonc/mdy425
Authors T. Kato1, S. Lee2, Y. Cheng3, G. Lee4, K. Lee5, A. Luft6, J. Trigo7, R. Hui8, B. Balint9, A. Robinson10, I. Okamoto11, G.J. Gerstner12, L. Paz-Ares13, X. Li14, Y. Shentu14, B. Piperdi14, A. Tafreshi15
  • 1Division Of Thoracic Oncology, Kanagawa Cancer Center, 2410815 - Yokohama/JP
  • 2Department Of Hematology And Oncology, Inje University College of Medicine, Busan/KR
  • 3Department Of Oncology, Cancer Hospital of Jilin Province, Changchun/CN
  • 4Divisions Of Hematology And Oncology, Department Of Internal Medicine, Institute of Health Science, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju/KR
  • 5Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju/KR
  • 6Department Of Oncology, Leningrad Regional Clinical Hospital, St. Petersburg/RU
  • 7Medical Oncology Department, Hospital Universitario Virgen de la Victoria & IBIMA, Malaga/ES
  • 8Department Of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital/AU
  • 9Pulmonary Department, Csongrád Megyei Mellkasi Betegségek Szakkórháza, Deszk/HU
  • 10Department Of Oncology, Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston/CA
  • 11Research Institute For Diseases Of The Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka/JP
  • 12Hematology/oncology, Illinois CancerCare–Peoria, Peoria/US
  • 13Medical Oncology Department, University Hospital 12 de October, Madrid/ES
  • 14Department Of Oncology, Merck & Co., Inc., Kenilworth/US
  • 15Department Of Oncology, Wollongong Oncology and University of Wollongong, Wollongong/AU

Abstract

Background

Primary results from the global, randomized, double-blind, phase 3 KEYNOTE-407 study (NCT02775435) demonstrated superior OS, PFS, and ORR with pembrolizumab plus carboplatin and paclitaxel or nab-paclitaxel (chemo) in patients with previously untreated squamous NSCLC. Here we report results from the East Asia subgroup of KEYNOTE-407.

Methods

In KEYNOTE-407, patients with untreated metastatic squamous NSCLC were randomized 1:1 to carboplatin 6 mg/mL/min and paclitaxel 200 mg/m2 Q3W or nab-paclitaxel 100 mg/m2 weekly (investigator’s choice) plus pembrolizumab or saline placebo Q3W for 4 cycles followed by pembrolizumab or placebo Q3W for a total of 35 treatment cycles. Randomization was stratified by taxane (paclitaxel vs nab-paclitaxel), PD-L1 (tumor proportion score [TPS] <1% vs ≥ 1%), and region (East Asia vs other). Primary endpoints were OS and PFS (by blinded independent central review [BICR]); ORR by BICR was a secondary endpoint. For the East Asia subgroup, OS and PFS HRs were estimated using an unstratified Cox regression model; between-group difference in ORR was estimated using an unstratified Miettinen & Nurminen method.

Results

Of 559 patients randomized globally, 106 (19.0%) with largely similar baseline characteristics were enrolled from East Asia (pembrolizumab plus chemo, n = 54; placebo plus chemo, n = 52). After median follow-up of 6.7 (range, 0.5–18.9) mo among patients from East-Asia, median (95% CI) OS (16.6 [16.6–NR] mo vs 9.5 [7.5–NR] mo) and PFS (6.3 [5.3–10.2] mo vs 4.1 [3.5–5.2] mo) were longer in those who received pembrolizumab plus chemo vs placebo plus chemo, with HRs of 0.44 [95% CI, 0.22–0.89] and 0.49 [95% CI, 0.30–0.82], respectively. ORR was 63.0% vs 34.6%, respectively (ORR difference, 28.3% [95% CI, 9.3–45.4]). Grade ≥3 AEs occurred in 83.3% of patients in the pembrolizumab plus chemo arm vs 80.8% of those in the placebo plus chemo arm.

Conclusions

Consistent with overall results from KEYNOTE-407, pembrolizumab plus chemo extended OS and PFS, and almost doubled ORR vs placebo plus chemo in patients from East Asia with previously untreated metastatic squamous NSCLC. No new safety signals were observed.

Editorial acknowledgement

Sheri Arndt.

Clinical trial identification

MK-3475-407, NCT02775435.

Legal entity responsible for the study

Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

T. Kato: Grants, personal fees: Abbvie, Astellas, AZ, BI, BMS, Chugai, Eli Lilly, Kyowa Kirin, MSD (inc. for this study), Novartis, Ono, Parexel, Pfizer, Quintiles, Taiho, Roche, Merck Serono, Sumitomo Dainippon. K. Lee: Grants: MSD during the conduct of the study; Personal fees for advisory boards: BMS, MSD outside of the submitted work. R. Hui: Advisory board member: MSD, AstraZeneca, Roche, BMS, Novartis; Speaker honoraria: MSD, Novartis, AstraZeneca, Roche, BMS. B. Balint: No financial interests or arrangements with the sponsor that may bias the results of the study. A. Robinson: Grants: Bristol-Myers Squibb, Merck, Roche, AstraZeneca. I. Okamoto: Grant support: AstraZeneca during conduct of the study. Additional grant support, personal fees (honoraria): AstraZeneca, Ono, BMS, Chugai, Lilly, Taiho, Boehringer Ingelheim and Pfizer outside the submitted work. L. Paz-Ares: Grant and funding to institution for conduct of this study: MSD; Personal fees for advisory boards: MSD, BMS, AstraZeneca, Lilly, Pfizer, Merck-Serono, Roche, Amgen, Takeda, Incyte outside the submitted work. X. Li: Employee: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA Y. Shentu, B. Piperdi: Employee: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. All other authors have declared no conflicts of interest.