Anti–PD-1 Monoclonal Antibody Plus Chemotherapy for Advanced Squamous NSCLC
Posted: Friday, June 4, 2021
Patients with advanced squamous non–small cell lung cancer (NSCLC) may benefit from first-line treatment with tislelizumab plus chemotherapy versus chemotherapy alone, according to Jie Wang, MD, PhD, of the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, and colleagues. The findings of the multicenter phase III RATIONALE 307 trial, which were published in JAMA Oncology, revealed this combination seemed to significantly improve progression-free survival and objective response rates with manageable toxicities.
“Tislelizumab, a monoclonal antibody with high binding affinity to the PD-1 receptor, was specifically engineered to minimize Fcγ receptor binding on macrophages, thereby abrogating antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti–PD-1 therapy,” the investigators commented.
In a 1:1:1 ratio, a total of 360 patients with treatment-naive stage IIIB to IV disease were randomly assigned to receive tislelizumab plus paclitaxel and carboplatin (arm A), tislelizumab plus nab-paclitaxel and carboplatin (arm B), or paclitaxel plus carboplatin (arm C). Follow-up data were provided for a median of 8.6 months.
Compared with chemotherapy alone, tislelizumab plus chemotherapy was reported to have prolonged the duration of progression-free survival (for both arms A and B vs. C: P < .001). Higher objective response rates and longer durations of response were observed in arms A (72.5% and 8.2 months) and B (74.8% and 8.6 months) versus arm C (49.6% and 4.2 months). There did not seem to be an association between PD-L1 expression and progression-free survival or objective response rates.
A total of 12.5%, 29.7%, and 15.4% of patients in arms A, B, and C, respectively, discontinued treatment as a result of adverse events. In each arm, the most frequently reported adverse event of grade 3 or higher was decreased neutrophil levels. There were six treatment-related deaths; however, they did not seem to be solely attributed to tislelizumab.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.