Adding Platinum Doublet to Immunotherapy Combination in Advanced Lung Cancer
Posted: Wednesday, July 22, 2020
The addition of platinum-based chemotherapy to the checkpoint inhibitors durvalumab plus tremelimumab in the first-line treatment of patients with metastatic stage IV non–small cell lung cancer (NSCLC) did not improve overall survival, according to a presentation during the ASCO20 Virtual Scientific Program (Abstract 9502). However, platinum-based chemotherapy did appear to improve objective response rates and progression-free survival, although with greater toxicity.
“These data suggest that adding chemotherapy to PD-1 checkpoint inhibitor monotherapy may be beneficial in those with PD-L1 TPS ≥ 50%,” stated Natasha B. Leighl, MD, FASCO, of Princess Margaret Hospital, Toronto, Canada, and colleagues.
A total of 301 patients with stage IV metastatic squamous or nonsquamous NSCLC, EGFR/ALK wild-type, were enrolled in the study. Patients were administered four cycles of durvalumab plus tremelimumab or durvalumab plus tremelimumab with platinum-doublet chemotherapy (pemetrexed or gemcitabine). They also received ongoing durvalumab or durvalumab plus pemetrexed maintenance until disease progression. Dr. Leighl and colleagues aimed to determine overall survival, progression-free survival, objective response rates, and toxicity in patients receiving this treatment regimen with and without the platinum doublet.
At a median of 16.6 months of follow-up, the investigators reported no significant differences in overall survival for either treatment regimen (16.6 months with chemotherapy, 14.1 months without). However, the progression-free survival and objective response rates were improved with immunotherapy plus platinum chemotherapy; specifically, progression-free survival was 7.7 months versus 3.2 months, and the objective response rate was 28% versus 14%. In addition, tumor mutational burden plasma levels lower than 20 mut/Mb were associated with decreased survival, regardless of the treatment regimen.
As for toxicity, there were more grade ≥ 3 adverse events with platinum chemotherapy than without it (82% vs. 70%). However, immune-based adverse events, including endocrinopathy (21%), colitis (11%), and pneumonitis (6%), which were consistent between both treatment groups.
Disclosure: For full disclosures of the authors, visit coi.asco.org.
