Frontline Durvalumab/Chemotherapy Regimen Improves Survival in ES-SCLC

Luis Paz-Ares, MD

Luis Paz-Ares, MD

A statistically significant improvement in overall survival (OS) was demonstrated with durvalumab (Imfinzi), a PD-L1 inhibitor, combined with chemotherapy in patients with previously untreated extensive-stage small cell lung cancer (ES-SCLC), according to findings from the phase III CASPIAN trial.

Median OS was 13.0 months (95% CI, 11.5-14.8) with the durvalumab combination versus 10.3 months (95% CI, 9.3-11.2) with etoposide-platinum chemotherapy alone, translating to a 27% reduction in the risk of death (HR, 0.73; 95% CI, 0.591-0.909;P= .0047). The 12-month and 18-month survival rates also improved with the PD-L1 inhibitor.

“The clinical benefit was observed across all efficacy endpoints,” lead investigator Luis Paz-Ares, MD, of 12 de Octubre University Hospital in Madrid, reported at the 2019 World Conference on Lung Cancer. “The safety findings were consistent with the know safety profiles of all agents received. 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.”

For more than 3 decades, etoposide with cisplatin or carboplatin has represented first-line treatment for patients with ES-SCLC, and few alternatives existed. Etoposide-platinum combinations produce high initial response rates, but the responses usually are not durable, Paz-Ares said. Relapse usually occurs within 6 months and median OS is about 10 months.

Immune checkpoint inhibitors have demonstrated clinical activity in ES-SCLC in several different studies, particularly in the first-line setting. Continuing that line of investigation, the CASPIAN trial evaluated durvalumab with or without the CTLA-4 inhibitor tremelimumab plus chemotherapy. Both arms were compared with platinum-etoposide chemotherapy alone. Patients assigned to chemotherapy alone could undergo prophylactic cranial irradiation (PCI) at their treating physician’s discretion.

Paz-Ares said an interim analysis showed a significant advantage for the durvalumab-chemotherapy arm (without tremelimumab) versus chemotherapy alone. His presentation focused on data from that comparison. Follow-up continues in the tremelimumab arm. The primary endpoint for the overall trial was OS.

Data analysis included 268 patients randomized to durvalumab-chemotherapy and 269 treated with chemotherapy alone. The patients had a median age of 62-63, men accounted for about 70% of the patients, about 45% were current smokers, about 47% were former smokers, and 10% of the patients had brain or CNS metastases. PCI was administered to 8% of patients in the etoposide-platinum arm.

The 12-month OS rate was 53.7% in the durvalumab arm and 39.8% with chemotherapy alone, and the 18-month OS rate was 33.9% with durvalumab and 24.7% without. Subgroup analysis demonstrated a consistent benefit for the durvalumab-chemotherapy arm.

Median progression-free survival (PFS) was similar between the 2 arms (5.1 months with durvalumab, 5.4 months without). Analysis of the 12-month PFS rate showed a large advantage favoring durvalumab (17.5% vs 4.7%).

Objective response rates were 67.9% for the durvalumab plus chemotherapy group and 57.6% for patients who received only chemotherapy, representing a 56% increase in the likelihood of response with the addition of durvalumab to chemotherapy. The median duration of response was identical in the 2 treatment arms (5.1 months), but 12-month response rates were 22.7% with durvalumab versus 6.3% with chemotherapy alone.

The two treatment arms had similar safety profiles. Any-grade all-cause adverse events (AEs), grade 3/4 AEs, serious AEs, AEs leading to treatment discontinuation, and AEs leading to death occurred in a similar proportion of patients in the 2 treatment groups. Not surprisingly, Paz-Ares noted, immune-related AEs occurred more often with durvalumab (19.6%) than with chemotherapy alone (2.6%).

Invited discussant Myung-Ju Ahn, MD, of Sungkyunkwan University in Seoul, South Korea, agreed with Paz-Ares that the trial results establish durvalumab plus etoposide-platinum chemotherapy as a new standard for ES-SCLC. The findings also confirmed the role of immune checkpoint blockade in ES-SCLC, she added, noting that the findings were consistent with those of the previously reportedIMpower133 trialthat compared etoposide-carboplatin chemotherapy with or without atezolizumab (Tecentriq).

Ahn said the nearly 3-month improvement in OS with durvalumab and chemotherapy also continues the history of relatively modest incremental improvement in outcomes for patients with ES-SCLC. She said research must go on to identify new and novel therapeutic approaches that might offer the potential for greater improvement in outcomes.

Reference:

L. Paz-Ares, Y. Chen, N. Reinmuth, et al. Overall survival with durvalumab plus etoposide-platinum in first-line extensive-stage SCLC: results from the CASPIAN study. Presented at: IASLC 20th World Conference on Lung Cancer; September 7-10, 2019; Barcelona, Spain. Abstract OA02.02.