Pembrolizumab plus docetaxel safe, effective in advanced NSCLC
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Pembrolizumab in combination with docetaxel substantially improved overall response rate and PFS compared with docetaxel alone among patients with non-small cell lung cancer whose disease progressed after platinum-based chemotherapy, according to results of a randomized phase 2 study published in JAMA Oncology.
The combination appeared well-tolerated overall and effective for patients with or without EGFR variations, researchers noted.
“Unfortunately, despite the overwhelming evidence for the use of immunotherapy in clinical practice, access to immune checkpoint inhibitors poses significant challenges and, as a result, many patients do not receive them as first-line treatment,” Oscar Arrieta, MD, MSc, chair of the thoracic oncology unit at Instituto Nacional de Cancerología in Mexico City, and colleagues wrote. “Docetaxel and platinum-based chemotherapy with or without bevacizumab [Avastin, Genentech] are additional options for patients with NSCLC who do not have access to immunotherapy. Unfortunately, the use of docetaxel with or without ramucirumab [Cyramza, Eli Lilly] or nintedanib [Ofev, Boehringer Ingelheim] has yielded low ORR of less than 25% and limited OS outcomes in previous studies.”
Arrieta and colleagues sought to determine the safety and efficacy of the anti-PD-1 therapy pembrolizumab (Keytruda, Merck) plus chemotherapy among immunotherapy-naive patients with NSCLC and disease progression after platinum-based chemotherapy.
The researchers randomly assigned 78 patients with histologically confirmed advanced NSCLC, regardless of EGFR variants or PD-L1 status, to pembrolizumab in combination with docetaxel (n = 40; mean age, 50.1 years; 48% men or docetaxel monotherapy (n = 38; mean age, 62.1 years; 34% men).
Among all patients, 34 were never smokers and 25 had an EGFR/ALK alteration.
Patients in the combination group received docetaxel dosed at 75 mg/m2 on day 1 and pembrolizumab dosed at 200 mg on day 8 every 3 weeks for up to six cycles, followed by pembrolizumab maintenance therapy until progression or unacceptable toxicity.
ORR served as the primary endpoint. PFS, OS and safety served as secondary endpoints.
Median follow-up was 8.9 months (95% CI, 4.2-15.9) for the combination group and 7.9 months (95% CI, 3.9-16.9) for the docetaxel monotherapy group.
Results showed a significant difference in ORR, assessed by an independent reviewer, between the combination and monotherapy groups (42.5% vs. 15.8%; OR = 3.94; 95% CI, 1.34-11.54). Researchers observed differences in ORR among patients without EGFR variations (35.7% in the combination group vs. 12% in the monotherapy group), as well as among those with EGFR variations (58.3% vs. 23.1%).
Additionally, patients in the combination group achieved longer PFS than those in the monotherapy group (9.5 months vs. 3.9 months; HR = 0.24; 95% CI, 0.13-0.46). This included patients without EGFR variations (9.5 months vs. 4.1 months; P < .001) and patients with EGFR variations (6.8 months vs. 3.5 months; P = .04).
Nine patients in the combination group and two patients in the monotherapy group experienced grade 1 or grade 2 pneumonitis (P = .03). Eleven patients in the combination group and one patient in the monotherapy group experienced any-grade hypothyroidism (P = .002). Researchers reported no new safety signals.
Use of docetaxel — which represented the second-line standard of care during the study’s design — for the control group served as a limitation to this study.
“This [study] highlights the potential role for this therapeutic combination in the second-line setting and warrants the design of larger, phase 3 trials that use immunotherapy as the control,” Arrieta and colleagues wrote. – by John DeRosier
Disclosures: Arrieta reports research funding from Merck Sharp & Dohme, grants and personal fees from AstraZeneca, Merck Sharp & Dohme and Roche, and personal fees from Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Pfizer and Takeda. Please see the study for all other authors’ relevant financial disclosures.
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