In the phase 3 CCTG BR.34 trial, no additional effect on overall survival (OS) was observed by adding platinum-based chemotherapy to dual checkpoint inhibition in first-line advanced or metastatic con-small cell lung cancer (NSCLC), researchers reported at the virtual meeting of the American Society of Clinical Oncology.
The international, open-label, randomized CCTG BR.34 trial accrued 301 participants from Canada and Australia, with stage IV NSCLC, EGFR/ALK wildtype, ECOG PS 0/1. Patients were randomized to receive either durvalumab (1500 mg IV) plus tremelimumab (75 mg IV) for four cycles followed by durvalumab maintenance until disease progression or the same plus chemotherapy. Patients with squamous carcinoma received gemcitabine-based treatment, patients with non-squamous received pemetrexed-based therapy, including pemetrexed maintenance in addition to immunotherapy.
“At a median follow up of 16.6 months, no significant difference in OS was seen between the two treatment arms”, reported Natasha Leighl, Clinician Investigator, Princess Margaret Cancer Centre, Toronto, Canada. Median OS was16.6 months with durvalumab/tremelimumab/chemo versus 14.1 months with durvalumab/tremelimumab (HR 0.88, 90% CI: 0.67-1.16; P=0.46). “There were some interesting trends, including [subgroups stratified] by sex, the presence of brain metastases, and pathologic subtype, but none of these were significant.”
Median progression-free survival (PFS), however, was significantly improved in the durvalumab/tremelimumab/chemotherapy arm at 7.7 versus 3.2 months (HR 0.67; 95% CI: 0.52-0.88; P=0.0035), as was the objective response rate at 28% versus 14%, (odds ratio 2.51; 95% CI: 1.36-4.63; P=0.003). The addition of chemotherapy significantly increased toxicity, in particular for classically recognized side effects such as myelosuppression, nausea and vomiting, fever, both neutropenic and non-neutropenic, neuropathy, and alopecia. Grade 3 or higher adverse events were reported in 82% and 70% of patients, in the durvalumab/tremelimumab/chemotherapy arm and the durvalumab/tremelimumab arms, respectively.
Leighl NB, et al. ASCO 2020 virtual meeting, abstract 9502.