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J Clin Oncol. 2019 Jan 8:JCO1800149. doi: 10.1200/JCO.18.00149. [Epub ahead of print]

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater.

Author information

1
Lung Clinic Grosshansdorf, Airway Research Center North, Grosshansdorf, Germany.
2
Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.
3
Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, Ontario, Canada.
4
Westmead Hospital and the University of Sydney, Sydney, NSW, Australia.
5
Jász-Nagykun-Szolnok County Hospital, Szolnok, Hungary.
6
Országos Korányi Pulmonológiai Intézet, Budapest, Hungary.
7
Meir Medical Center, Kfar-Saba, Israel.
8
The Cancer Institute, Soroka Medical Center and Ben-Gurion University, Beer-Sheva, Israel.
9
Wollongong Oncology and University of Wollongong, Wollongong, NSW, Australia.
10
St James's Hospital and Cancer Trials Ireland, Dublin, Ireland.
11
The Royal Marsden Hospital, Sutton, Surrey, United Kingdom.
12
MedStar Franklin Square Hospital, Baltimore, MD.
13
Okayama University Hospital, Okayama, Japan.
14
MSD, Brussels, Belgium.
15
Merck & Co., Inc., Kenilworth, NJ.
16
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD.

Abstract

PURPOSE:

In the randomized, open-label, phase III KEYNOTE-024 study, pembrolizumab significantly improved progression-free survival and overall survival (OS) compared with platinum-based chemotherapy in patients with previously untreated advanced non-small-cell lung cancer (NSCLC) with a programmed death ligand 1 tumor proportion score of 50% or greater and without EGFR/ALK aberrations. We report an updated OS and tolerability analysis, including analyses adjusting for potential bias introduced by crossover from chemotherapy to pembrolizumab.

PATIENTS AND METHODS:

Patients were randomly assigned to pembrolizumab 200 mg every 3 weeks (for up to 2 years) or investigator's choice of platinum-based chemotherapy (four to six cycles). Patients assigned to chemotherapy could cross over to pembrolizumab upon meeting eligibility criteria. The primary end point was progression-free survival; OS was an important key secondary end point. Crossover adjustment analysis was done using the following three methods: simplified two-stage method, rank-preserving structural failure time, and inverse probability of censoring weighting.

RESULTS:

Three hundred five patients were randomly assigned (pembrolizumab, n = 154; chemotherapy, n = 151). At data cutoff (July 10, 2017; median follow-up, 25.2 months), 73 patients in the pembrolizumab arm and 96 in the chemotherapy arm had died. Median OS was 30.0 months (95% CI, 18.3 months to not reached) with pembrolizumab and 14.2 months (95% CI, 9.8 to 19.0 months) with chemotherapy (hazard ratio, 0.63; 95% CI, 0.47 to 0.86). Eighty-two patients assigned to chemotherapy crossed over on study to receive pembrolizumab. When adjusted for crossover using the two-stage method, the hazard ratio for OS for pembrolizumab versus chemotherapy was 0.49 (95% CI, 0.34 to 0.69); results using rank-preserving structural failure time and inverse probability of censoring weighting were similar. Treatment-related grade 3 to 5 adverse events were less frequent with pembrolizumab compared with chemotherapy (31.2% v 53.3%, respectively).

CONCLUSION:

With prolonged follow-up, first-line pembrolizumab monotherapy continues to demonstrate an OS benefit over chemotherapy in patients with previously untreated, advanced NSCLC without EGFR/ALK aberrations, despite crossover from the control arm to pembrolizumab as subsequent therapy.

PMID:
30620668
DOI:
10.1200/JCO.18.00149

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