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Original Investigation
April 9, 2020

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

Author Affiliations
  • 1Thoracic Oncology Unit, Laboratory of Experimental Oncology, National Cancer Institute (INCan), Mexico City, Mexico
  • 2Clinical and Translational Oncology Group, Clínica del Country, Bogotá, Colombia
  • 3Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia
  • 4Molecular Oncology and Biology Systems Research Group (G-FOX), Universidad el Bosque, Bogotá, Colombia
  • 5Hospital de Oncología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
  • 6Servicio de Oncología Médica, Centro Médico Nacional 20 de Noviembre, Mexico City, Mexico
  • 7Departamento de Oncología, Centro Médico ABC, Mexico City, Mexico
  • 8Thoracic Medical Oncology and Early Clinical Trials, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore
  • 9Molecular and Cellular Oncology Laboratory, Germans Trias i Pujol Research Institute and Hospital (IGTP), Barcelona, Spain
JAMA Oncol. 2020;6(6):856-864. doi:10.1001/jamaoncol.2020.0409
Key Points

Question  Can a combination of immunotherapy and chemotherapy provide clinical benefits in immunotherapy-naive patients with disease progression after treatment with platinum-based chemotherapy?

Findings  In this phase 2 randomized clinical trial of 78 patients with non–small cell lung cancer (NSCLC), the combination of pembrolizumab plus docetaxel was well tolerated and substantially improved overall response rate and progression-free survival in patients with advanced disease and progression after platinum-based chemotherapy, including NSCLC with EGFR variations.

Meaning  Results suggest that the combination of pembrolizumab and docetaxel in previously treated NSCLC improves overall response rate and progression-free survival irrespective of programmed cell death ligand 1 or EGFR variation status, highlighting the potential role for this therapeutic combination in the second-line setting; these findings warrant further evaluation compared with immunotherapy.


Importance  Because of socioeconomic factors, many patients with advanced non–small cell lung cancer (NSCLC) do not receive immunotherapy in the first-line setting. It is unknown if the combination of immunotherapy with chemotherapy can provide clinical benefits in immunotherapy-naive patients with disease progression after treatment with platinum-based chemotherapy.

Objective  To evaluate the safety and efficacy of the combination of pembrolizumab plus docetaxel in patients with previously treated advanced NSCLC following platinum-based chemotherapy regardless of EGFR variants or programmed cell death ligand 1 status.

Design, Setting, and Participants  The Pembrolizumab Plus Docetaxel for Advanced Non–Small Cell Lung Cancer (PROLUNG) trial randomized 78 patients with histologically confirmed advanced NSCLC in a 1:1 ratio to receive either pembrolizumab plus docetaxel or docetaxel alone from December 2016 through May 2019.

Interventions  The experimental arm received docetaxel on day 1 (75 mg/m2) plus pembrolizumab on day 8 (200 mg) every 3 weeks for up to 6 cycles followed by pembrolizumab maintenance until progression or unacceptable toxic effects. The control arm received docetaxel monotherapy.

Main Outcomes and Measures  The primary end point was overall response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival, and safety.

Results  Among 78 recruited patients, 32 (41%) were men, 34 (44%) were never smokers, and 25 (32%) had an EGFR/ALK alteration. Forty patients were allocated to receive pembrolizumab plus docetaxel, and 38 were allocated to receive docetaxel. A statistically significant difference in ORR, assessed by an independent reviewer, was found in patients receiving pembrolizumab plus docetaxel vs patients receiving docetaxel (42.5% vs 15.8%; odds ratio, 3.94; 95% CI, 1.34-11.54; P = .01). Patients without EGFR variations had a considerable difference in ORR of 35.7% vs 12.0% (P = .06), whereas patients with EGFR variations had an ORR of 58.3% vs 23.1% (P = .14). Overall, PFS was longer in patients who received pembrolizumab plus docetaxel (9.5 months; 95% CI, 4.2-not reached) than in patients who received docetaxel (3.9 months; 95% CI, 3.2-5.7) (hazard ratio, 0.24; 95% CI, 0.13-0.46; P < .001). For patients without variations, PFS was 9.5 months (95% CI, 3.9-not reached) vs 4.1 months (95% CI, 3.5-5.3) (P < .001), whereas in patients with EGFR variations, PFS was 6.8 months (95% CI, 6.2-not reached) vs 3.5 months (95% CI, 2.3-6.2) (P = .04). In terms of safety, 23% (9 of 40) vs 5% (2 of 38) of patients experienced grade 1 to 2 pneumonitis in the pembrolizumab plus docetaxel and docetaxel arms, respectively (P = .03), while 28% (11 of 40) vs 3% (1 of 38) experienced any-grade hypothyroidism (P = .002). No new safety signals were identified.

Conclusions and Relevance  In this phase 2 study, the combination of pembrolizumab plus docetaxel was well tolerated and substantially improved ORR and PFS in patients with advanced NSCLC who had previous progression after platinum-based chemotherapy, including NSCLC with EGFR variations.

Trial Registration  ClinicalTrials.gov Identifier: NCT02574598

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