Janice M. Mehnert
Pembrolizumab appeared safe and effective for patients with pretreated PD-L1-positive small cell lung cancer, according to data from the phase 1b KEYNOTE-028 study published in Journal of Clinical Oncology.
Pembrolizumab (Keytruda, Merck) is a highly selective humanized monoclonal antibody that binds to the PD-1 receptor and directly blocks the interaction between PD-1 and its ligands.
The agent has demonstrated robust antitumor activity with a favorable safety profile in a variety of malignancies.
Researchers designed the multicohort, open-label phase 1b KEYNOTE-028 trial to evaluate the efficacy and safety of pembrolizumab among patients with PD-L1-positive tumors.
“Immunotherapy is quickly becoming an important therapeutic tool in the treatment of many different types of tumors,” Janice M. Mehnert, MD, medical oncologist and director of the phase 1 and developmental therapeutics program at Rutgers Cancer Institute of New Jersey, told HemOnc Today. “This is one of the earliest trials of checkpoint inhibitors [among] patients with small cell lung cancer.”
Twenty-four patients (median age, 60.5 years; men, 58.3%) with extensive-stage small cell lung cancer received 10 mg/kg pembrolizumab every 2 weeks over 24 months until disease progression, intolerable toxicity, physician decision to discontinue or withdrawal of consent.
Safety, tolerability and objective response rate served as the primary endpoints. Secondary endpoints included PFS, OS and duration of response.
Median follow-up was 9.8 months.
Researchers reported an ORR of 33.3% (95% CI, 15.6-55.3), which include one patient with a complete response, seven patients with partial responses and one patient with stable disease for less than 6 months.
Median time to response was 2 months, and median duration of response was 19.4 months. Three patients remained on treatment with ongoing responses at data cutoff.
Median PFS was 1.9 months (95% CI, 1.7-5.9); 28.6% of patients achieved 6-month PFS and 23.8% achieved 12-month PFS.
Median OS was 9.7 months (95% CI, 4.1 to not reached). Researchers reported a 66% 6-month rate and 37.7% 12-month rate.
All patients experienced adverse events, including asthenia (n = 7), fatigue (n = 7), cough (n = 6), arthralgia (n = 5), diarrhea (n = 5), insomnia (n = 5) and rash (n = 5).
Eight patients (33.3%) experienced grade 3 to grade 5 adverse events, two of which researchers considered to be treatment related.
“This study shows that immunotherapy has activity in a population of patients with pretreated disease, usually a difficult population to treat,” Mehnert said. “The next steps are to learn how to further optimize this therapy for the treatment of [patients with small cell lung cancer].”
Mehnert noted additional studies of pembrolizumab for this patient population are ongoing.
“Building on the findings of this study, a number of clinical trials have been launched at Rutgers Cancer Institute and elsewhere that aim to more accurately define which [patients with small cell lung cancer] are more likely to respond to pembrolizumab,” Mehnert said. “Others aim to explore the safety and efficacy of pembrolizumab when combined with other modes of treatment including chemotherapy, radiation and other immunotherapy regimens.” – by Kristie L. Kahl
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, can be reached at Rutgers Cancer Institute of New Jersey, 195 Little Albany St., New Brunswick, NJ 08903-2681.
Disclosures: Mehnert reports honoraria from EMD Serono, Genentech and Merck; research funding from Amgen, AstraZeneca, Immunoore, Merck, Novartis, Polymona and Sanofi; and travel, accommodations and expenses from EMD Serono and Merck. Please see the full study for a list of all other authors’ relevant financial disclosures.