In the single-institution phase II PROLUNG trial reported in JAMA Oncology, Oscar Arrieta, MD, and Christian Rolfo, MD, PhD, and colleagues found that the addition of pembrolizumab to docetaxel improved objective response rates and progression-free survival in immunotherapy-naive patients with advanced non–small cell lung cancer (NSCLC) who experienced disease progression after first-line platinum-based chemotherapy.1 Dr. Arrieta is with the Laboratory of Experimental Oncology, National Cancer Institute, Mexico City. Dr. Rolfo is with the Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore.
Oscar Arrieta, MD
Christian Rolfo, MD, PhD
The open-label trial included 78 patients at the National Cancer Institute, Mexico City. Patients were randomly assigned between December 2016 and May 2019 to receive docetaxel at 75 mg/m2 on day 1 plus 200 mg of pembrolizumab on day 8 every 3 weeks for up to six cycles followed by pembrolizumab maintenance (n = 40), until disease progression or unacceptable toxic effects, or docetaxel alone (n = 38).
Patients were enrolled regardless of EGFR variants or programmed cell death ligand 1 status. A total of 25 patients (32%) had EGFR alterations (12 in the pembrolizumab/docetaxel group and 13 in docetaxel-alone group). The primary endpoint was overall response rate on independent review.
Objective response was observed in 42.5% of patients in the pembrolizumab/docetaxel group vs 15.8% of the docetaxel-alone group (odds ratio [OR] = 3.94, P = .01). Response rates were 35.7% vs 12.0% (P = .06) among patients without EGFR alterations and 58.3% vs 23.1% (P = .14) among those with EGFR alterations.
Among all patents, median progression-free survival was 9.5 months vs 3.9 months (hazard ratio [HR] = 0.24, P < .001). Median progression-free survival was 9.5 months vs 4.1 months among patients without EGFR alterations (P < .001) and 6.8 months vs 3.5 months among those with EGFR alterations (P = .04).
Among any-grade non–immune-related adverse events in the pembrolizumab/docetaxel vs docetaxel-alone groups, significant differences in incidence were observed for hypomagnesemia (0% vs 18%, P = .004) and lymphopenia (20% vs 0%, P = .004). Pneumonitis (all grade 1 or 2) occurred in 23% vs 5% of patients (P = .03), and any-grade hypothyroidism occurred in 28% vs 3% (P = .002). Adverse events led to treatment discontinuation in three vs no patients.
"The combination of pembrolizumab plus docetaxel was well tolerated and substantially improved overall response rate and progression-free survival in patients with advanced NSCLC."— Oscar Arrieta, MD, Christian Rolfo, MD, PhD, and colleagues
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The investigators concluded: “In this phase II study, the combination of pembrolizumab plus docetaxel was well tolerated and substantially improved overall response rate and progression-free survival in patients with advanced NSCLC who had previous progression after platinum-based chemotherapy, including NSCLC with EGFR variations.”
DISCLOSURE: The study was funded by Merck Sharp & Dohme. Dr Arrieta reported receiving grants from Merck Sharp & Dohme during the conduct of the study; grants and personal fees from AstraZeneca, Merck Sharp & Dohme, and Roche; and personal fees from Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Co, Pfizer, and Takeda outside the submitted work. Dr Rolfo reported receiving research grants at Antwerp University Hospital, Belgium, from Novartis and Sanofi; receiving speaker fees from Guardant Health, Merck Sharp & Dohme, and Novartis; receiving scientific advisor fees from Mylan; serving on a steering scientific committee for Oncompass; and participating in research collaborations for OncoDNA and Biomark Inc., during the conduct of the study. For full disclosures of all study authors, visit jamanetwork.com.
1. Arrieta O, Barron F, Ramirez-Tirado LA, et al: Efficacy and safety of pembrolizumab plus docetaxel vs docetaxel alone in patients with previously treated advanced non-small cell lung cancer. The PROLUNG phase 2 randomized clinical trial. JAMA Oncol. April 9, 2020 (early release online).