The addition of durvalumab to standard chemotherapy continued to demonstrate an improvement in overall survival for patients with treatment-naïve extensive-stage small cell lung cancer.
Updated results from the phase 3 CASPIAN study, presented at the 2020 ASCO Virtual Scientific Program, suggested that the addition of durvalumab (Imfinzi) to standard chemotherapy continued to demonstrate an improvement in overall survival (OS) for patients with treatment-naïve extensive-stage small cell lung cancer (ES-SCLC).1
According to principal investigator Luis Paz-Ares, MD, PhD, who presented the data at ASCO, the findings solidify the use of the PD-L1 inhibitor in combination with etoposide plus either cisplatin or carboplatin (EP) as a new frontline standard of care for this patient population.
“This is an effective first-line treatment in the extensive-stage setting, where improving outcomes has been a challenge and so few patients survive 5 years,” Paz-Ares, chair of the Medical Oncology Department at the Hospital Universitario Doce de Octubre in Madrid, Spain, said in a press release from AstraZeneca, the manufacturer of durvalumab.2
After a median follow-up of 25.1 months, the median OS was 12.9 months (95% CI, 11.3-14.7) among patients who received durvalumab plus EP compared with 10.5 months (95% CI, 9.3-11.2) for those who received EP alone, which translated into an HR of 0.75 (95% CI, 0.62-0.91; nominal P = .0032). Ultimately, the OS data favored the use of durvalumab, whether carboplatin (HR, 0.79; 95% CI, 0.63-0.98) or cisplatin (HR, 0.67; 95% CI, 0.46-0.97) was used.
“Importantly, the separation among the curves seems to be observed over time and, indeed, survival at 2 years improves from 14% [of participants] in the control arm to 22% on the experimental arm,” Paz-Ares noted. “The magnitude of the benefit is very similar and very consistent across all the prespecified subgroups of patients analyzed, including those treated with cisplatin or those patients with liver or brain metastases.”
Approximately two-thirds of patients diagnosed with small cell lung cancer have extensive-stage disease and, although nearly 80% of patients initially respond to EP therapy, most relapse within 6 months, according to Paz-Ares and colleagues. Historically though, the median OS has been about 10 months.3
In March 2020, the FDA approved durvalumab in combination with EP as first-line therapy for ES-SCLC based on interim findings from CASPIAN showing that, after a median follow-up of 14.2 months, the addition of the immunotherapy agent improved median OS to 13.0 months versus 10.3 months with EP alone (HR, 0.73; 95% CI, 0.59-0.91; P = 0.0047).3,4
The approval marked another benchmark for incorporating immunotherapy directed at the PD-1/PD-L1 pathway into the treatment paradigm for small cell lung cancer; the introduction of these agents over the past 2 years has improved OS in the frontline setting after more than 3 decades of limited progress, said Paz-Ares.
However, though the CASPIAN findings support the durvalumab regimen, the study also tested a dual immunotherapy combination plus EP that did not meet a prespecified threshold for statistical significance (P ≤ 0.0418). The combination of durvalumab plus tremelimumab, an investigational CTLA-4 immune checkpoint inhibitor, and EP demonstrated a median OS of 10.4 months (95% CI, 9.6-12.0) versus 10.5 months (95% CI, 9.3-11.2) for EP alone (HR, 0.82; 95% CI, 0.68-1.00; P = 0.0451).
1.Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab ± tremelimumab + platinum-etoposide in first-line extensive-stage SCLC (ES-SCLC): updated results from the phase III CASPIAN study. J Clin Oncol. doi: 10.1200/JCO.2020.38.
2. Imfinzi showed a sustained overall survival benefit in 1st-line extensive-stage small cell lung cancer in the phase III CASPIAN trial. News release. AstraZeneca. Published May 29, 2020. Accessed May 29, 2020. bit.ly/3gCj6ss
3. FDA approves durvalumab for extensive-stage small cell lung cancer. FDA. Published March 30, 2020. Accessed May 29, 2020. fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-extensive-stage-small-cell-lung-cancer.
4. Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. doi:10.1016/S0140-6736(19)32222-6