Pembrolizumab, chemoradiation therapy show antitumor activity in locally advanced NSCLC
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Use of pembrolizumab alongside chemoradiation therapy induces antitumor activity in previously untreated unresectable, locally advanced stage III non-small cell lung cancer, according to a presenter at the virtual 2021 ASCO Annual Meeting.
“The standard of care for patients with unresectable, locally advanced stage III non-small cell lung cancer (NSCLC) includes concurrent chemoradiation therapy (cCRT) followed by consolidation therapy with durvalumab,” Salma K. Jabbour, MD, vice chair of clinical research & faculty development and clinical chief, radiation oncology at RWJUH/Rutgers Cancer Institute, said in the presentation. “However, approximately 22% to 30% of patients who begin chemoradiation therapy experience disease progression or toxicity and are ineligible to receive durvalumab as consolidation therapy, representing an unmet clinical need.”
The KEYNOTE-799 study, a nonrandomized phase 2 study of pembrolizumab and cCRT, served to determine objective response rate with RECIST v1.1, incidence rate of grade 3 or higher pneumonitis, and safety and efficacy of treatment, according to the abstract. Participants included 216 patients aged at least 18 years with untreated, unresectable local stage III NSCLC. In the first portion of KEYNOTE-799, a cutoff of July 31, 2020, was set 6 months after the previous cutoff. The presentation detailed 3 additional months of follow-up data from KEYNOTE-799 participants.
Two cohorts were established in the study: cohort A (n = 112) included squamous and nonsquamous NSCLC and cohort B (n = 104) included nonsquamous only. All participants received treatment except two from cohort B.
“In cohort A, patients received pembrolizumab, paclitaxel and carboplatin for one cycle followed by pembrolizumab, paclitaxel, carboplatin and definitive thoracic radiotherapy to 60 Gy followed by consolidated pembrolizumab for cycles 4 to 17,” Jabbour said. “In cohort B, patients received the same sequence of therapy but with pembrolizumab, pemetrexed and cisplatin.”
The ORR was 70.5% in cohort A and 70.6% in cohort B, but the median duration of response was not determined in the set timeframe, Jabbour said in the presentation. Based on Kaplan-Meier analysis, 80% of cohort A and 76% of cohort B were expected to have a response duration of 12 months or longer. According to the abstract, ORR did not differ due to PD-L1 status and tumor histology.
Additionally, the incidence of grade 3 or greater pneumonitis occurred in nine cohort A patients (8%) and seven cohort B patients (6.9%), and grade 3 to 5 treatment-related adverse events occurred in 64.3% and 50% of cohort A and B participants, respectively.
“Pembrolizumab plus concurrent chemoradiation therapy represents a promising therapy for patients with previously untreated, locally advanced, stage III non-small cell lung cancer,” Jabbour said. “Pembrolizumab plus concurrent chemoradiation therapy followed by pembrolizumab with or without olaparib versus concurrent chemoradiation therapy followed by durvalumab is being investigated in the phase III KEYLYNK-012 study in the setting of stage III non-small cell lung cancer.”
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Jabbour SK, et al. Abstract 8512. Presented at: 2021 ASCO Annual Meeting (virtual meeting); June 4-8, 2021.
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