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Combining durvalumab with standard frontline chemotherapies showed a sustained overall survival benefit in patients with extensive-stage small cell lung cancer, but a regimen of durvalumab, chemotherapy, and tremelimumab did not boost OS.
José Baselga, MD, PhD
Combining durvalumab with standard frontline chemotherapies showed a sustained overall survival (OS) benefit in patients with extensive-stage small cell lung cancer (ES-SCLC), according to results from the final analysis of the phase III CASPIAN trial; however, the study missed its coprimary endpoint, as the combination of durvalumab with chemotherapy and tremelimumab did not induce a statistically significant improvement in OS compared with standard chemotherapy alone.1
No new safety signals emerged with this final analysis. The data will be presented at an upcoming medical meeting, AstraZeneca, the developer of durvalumab and tremelimumab, reported in a press release.
“We are pleased to see the sustained and meaningful survival benefit of Imfinzi for patients with small cell lung cancer after more than 2 years’ median follow up. We have already received the first global regulatory approval for Imfinzi with etoposide plus either carboplatin or cisplatin and remain on track for more approvals soon as we provide patients an important new first-line treatment option,” José Baselga, MD, PhD, executive vice president, Oncology R&D, AstraZeneca, said in the press release.
Based on the primary CASPIAN analysis, which showed that durvalumab plus standard-of-care chemotherapies induced a statistically significant improvement in OS compared with chemotherapy alone, the FDA previously granted a priority review designation to a supplemental Biologics License Application (sBLA) for durvalumab for the frontline treatment of patients with ES-SCLC.
The primary analysis demonstrated that adding durvalumab to chemotherapy reduced the risk of death by 27% compared with chemotherapy alone (HR, 0.73; 95% CI, 0.591-0.909; P = .0047).2 The median OS increased from 10.3 months (95% CI, 9.3-11.2) with etoposide/platinum chemotherapy alone to 13.0 months (95% CI, 11.5-14.8) with the addition of durvalumab.
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. An interim analysis showed a significant advantage for the durvalumab/chemotherapy arm (without tremelimumab) versus chemotherapy alone. Follow-up continues in the tremelimumab arm.
The interim analysis included 268 patients randomized to durvalumab/chemotherapy and 269 treated with chemotherapy alone. The patients had a median age of about 62 years, 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.
The 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%).
The 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 2 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, immune-related AEs occurred more often with durvalumab (19.6%) than with chemotherapy alone (2.6%).
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. Relapse usually occurs within 6 months and median OS is about 10 months.
A decision on the sBLA is expected from the FDA in the first of quarter of this year.