First-line durvalumab plus chemotherapy improves OS in extensive-stage small cell lung cancer
BARCELONA — The addition of durvalumab to platinum-etoposide chemotherapy significantly extended OS among patients with extensive-stage small cell lung cancer, according to results of the CASPIAN study presented at International Association for the Study of Lung Cancer World Conference on Lung Cancer.
“Small cell lung cancer is typically chemotherapy sensitive and responds well to chemotherapy; however, relapse and resistance usually happens quite early on in the treatment,” Luis Paz-Ares, MD, PhD, chair of the department of medical oncology at Hospital Universitario 12 de Octubre, H120-CNIO Lung Cancer Unit, associate professor at Universidad Complutense, and head of the lung cancer unit at the National Oncology Research Center in Madrid, said during a press conference. “Over the last 4 decades, we’ve been treating our patients with extensive disease, which represents about 70% of patients, with platinum-based chemotherapy. Over the last few years, we have shown that checkpoint inhibitors, particularly PD-L1 and PD-1 inhibitors, have activity in this setting, and the combination of chemotherapy plus checkpoint inhibitors may be especially effective.”
Paz-Ares and colleagues of the CASPIAN trial sought to evaluate the role of first-line durvalumab (Imfinzi, MedImmune/AstraZeneca), an anti-PD-L1 inhibitor, with or without the anti-CTLA-4 inhibitor tremelimumab (CP-675,206, AstraZeneca) plus etoposide and carboplatin or cisplatin in extensive-stage small cell lung cancer.
The study included 805 patients with treatment-naive extensive-stage small cell lung cancer with a WHO performance status of 0 to 1. Researchers did not exclude patients who had asymptomatic or treated and stable brain metastases.
Researchers assigned patients 1:1:1 to one of three treatment arms: 1,500 mg durvalumab plus chemotherapy for up to four cycles followed by 1,500 mg durvalumab every 4 weeks until disease progression; chemotherapy every 3 weeks for up to six cycles followed by optional prophylactic cranial irradiation; or 1,500 mg durvalumab plus 75 mg tremelimumab with chemotherapy every 3 weeks for up to four cycles followed by 1,500 mg durvalumab every 4 weeks until disease progression. Chemotherapy in each arm consisted of 80 mg/m2 to 100 mg/m2 etoposide with either carboplatin area under the curve 5 to 6 or 75 mg/m2 to 80 mg/m2 cisplatin.
OS served as the study’s primary endpoint. Secondary endpoints included PFS, objective response rate, safety and tolerability, and health-related quality of life.
The current analysis compares only the durvalumab-chemotherapy (n = 265) and chemotherapy-alone (n = 266) groups.
“A preplanned interim analysis by the independent monitoring committee showed that this comparison reached statistical significance at first follow-up that was set in the preplanned statistical analysis, which did not happen with the durvalumab-tremelimumab arm,” Paz-Ares said.
In total, 86.8% of patients in the durvalumab group received at least four cycles of chemotherapy, as did 84.6% of patients in the control group, with 56.8% of patients in the control group receiving the full six cycles. Patients assigned durvalumab received a median seven (range, 1-25) doses of the study drug.
Results showed a median OS of 13 months in the durvalumab group vs. 10.3 months in the chemotherapy group, which represented a statistically significantly 27% reduction in the risk for death (HR = 0.73; 95% CI, 0.59-0.9). More patients assigned durvalumab achieved OS at 1 year (53.7% vs. 39.8%) and 18 months (33.9% vs. 24.7%).
ORR also was higher in the durvalumab group, at 67.9% vs. 57.6% with chemotherapy (OR = 1.56; 95% CI, 1.09-2.21). Further, more patients assigned durvalumab remained in response at 12 months (22.7% vs. 6.3%).
A greater proportion of patients assigned durvalumab also achieved 1-year PFS (17.5% vs. 4.7%; HR = 0.78; 95% CI, 0.64-0.93).
Benefit occurred across patient subsets, including among those with brain metastases, Paz-Ares said.
Researchers did not identify any new safety signals with the durvalumab-chemotherapy regimen. Almost all patients in both groups experienced any-grade all-cause adverse events (durvalumab, 98.1%; chemotherapy, 97%), with grade 3 or grade 4 adverse events occurring among 61.5% in the durvalumab group and 62.4% of the chemotherapy group. In both groups, 9.4% of patients discontinued treatment due to adverse events.
Notably, 19.6% of patients in the durvalumab group experienced immune-mediated adverse events — about half of which were cases of thyroid dysfunction, and 5% of which were severe — compared with only 2.6% of patients in the chemotherapy group.
“Combining durvalumab with either cisplatin- or carboplatin-etoposide in extensive-stage small cell lung cancer provides an important new treatment option for patients and physicians,” Paz-Ares said. – by Alexandra Todak
Paz-Ares L, et al. Abstract PL02.11. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer; Sept. 7-10, 2019; Barcelona.
Disclosures: Paz-Ares reports consultant/advisory or speakers bureau roles with or research funding from AstraZeneca, Amgen, Bayer, Blueprint, Bristol-Myers Squibb, Eli Lilly, Genomica, Ipsen, Merck, Novartis, Roche and Sanofi. He also reports stock ownership in Altum Sequencing. Please see the abstract for all other authors’ relevant financial disclosures.