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Updated Results of CASPIAN Trial: Addition of Durvalumab With or Without Tremelimumab to Chemotherapy in Extensive-Stage SCLC


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As reported in The Lancet Oncology by Goldman et al, updated results from the phase III CASPIAN trial showed maintained improvement in overall survival with first-line durvalumab plus platinum/etoposide vs platinum/etoposide in patients with extensive-stage small cell lung cancer (SCLC). However, the addition of tremelimumab to durvalumab plus platinum/etoposide did not significantly improve outcomes vs platinum/etoposide.

The trial supported the March 2020 U.S. Food and Drug Administration approval of durvalumab for use in combination with etoposide and either carboplatin or cisplatin as first-line treatment of patients with extensive-stage SCLC.

Study Details

In the open-label international trial, 805 treatment-naive patients were randomly assigned 1:1:1 between March 2017 and May 2018 to receive durvalumab and tremelimumab plus platinum/etoposide (n = 268), durvalumab plus platinum/etoposide (n = 268), or platinum/etoposide (n = 269). The two primary endpoints were overall survival for durvalumab plus platinum/etoposide vs platinum/etoposide, and overall survival for durvalumab/tremelimumab plus platinum/etoposide vs platinum/etoposide in the intention-to-treat population.

At the previously reported interim analysis, durvalumab plus platinum/etoposide was associated with a significant improvement in overall survival vs platinum/etoposide, with a hazard ratio (HR) of 0.73 (P = .0047). As of data cutoff for the current analysis in January 2020, median follow-up for overall survival in censored patients was 25.1 months (interquartile range = 22.3–27.9 months), representing an additional 11 months of follow-up from the interim analysis. For the primary overall survival analysis of durvalumab/tremelimumab plus platinum/etoposide vs platinum/etoposide, statistical significance was set at a P value < .0418.

Overall Survival

In the primary analysis, median overall survival was 10.4 months (95% confidence interval [CI] = 9.6­–12.0 months) in the durvalumab/tremelimumab plus platinum/etoposide group vs 10.5 months (95% CI = 9.3–11.2 months) in the platinum/etoposide group (HR = 0.82, 95% CI = 0.68­–1.00; P = .045).

In the updated analysis, median overall survival was 12.9 months (95% CI = 11.3–14.7 months) in the durvalumab plus platinum/etoposide group vs 10.5 months (95% CI = 9.3–11.2 months) in the platinum/etoposide group (HR = 0.75, 95% CI = 0.62–0.91; nominal P = .0032).

Overall survival at 18 months was 30.7% (95% CI = 25.2%–36.4%) in the durvalumab/tremelimumab plus platinum/etoposide group and 32.0% (95% CI = 26.5%–37.7%) in the durvalumab plus platinum/etoposide group vs 24.8% (95% CI = 19.7%–30.1%) in the platinum/etoposide group. In post hoc analyses, 12- and 24-month overall survival rates were 43.8%, 52.8%, and 39.3%, respectively, and 23.4%, 22.2%, and 14.4%, respectively.

KEY POINTS

  • Durvalumab/tremelimumab plus platinum/etoposide did not significantly improve overall survival vs platinum/etoposide.
  • Durvalumab plus platinum/etoposide maintained overall survival benefit vs platinum/etoposide over longer-term follow-up.

Progression-Free Survival and Response Rates

Median progression-free survival was 4.9 months (95% CI = 4.7–5.9 months) in the durvalumab/tremelimumab plus platinum/etoposide group (HR = 0.84, 95% CI = 0.70–1.01 vs platinum/etoposide group), 5.1 months (95% CI = 4.7–6.2 months) in the durvalumab plus platinum/etoposide group (HR = 0.80, 95% CI = 0.66­–0.96 vs platinum/etoposide group), and 5.4 months (95% CI = 4.8–6.2 months) in the platinum/etoposide group. Rates at 6 and 12 months were 43.2%, 45.4%, and 45.8%, respectively, and 16.9%, 17.9%, and 5.3%, respectively. At post hoc analysis, rates at 24 months were 11.5%, 11.0%, and 2.9%, respectively.

In post hoc analyses, confirmed objective response was observed in 58% of the durvalumab/tremelimumab plus platinum/etoposide group (odds ratio [OR] = 1.02, 95% CI = 0.72–1.44 vs platinum/etoposide group), 68% of the durvalumab plus platinum/etoposide group (OR = 1.53, 95% CI = 1.08–2.18 vs platinum/etoposide group), and 58% of the platinum/etoposide group. The estimated percentages of responders remaining in response at 12 and 24 months were 24.9%, 23.2%, and 7.3%, respectively, and 17.2%, 13.5%, and 3.9%, respectively.

Safety Profiles

Safety profiles of the study regimens were consistent with those previously reported. The most common grade ≥ 3 adverse events in the three groups were neutropenia (32%, 24%, and 33%) and anemia (13%, 9%, and 18%). Serious adverse events were reported in 45%, 32%, and 36% of patients. Treatment-related deaths occurred in 5%, 2%, and 1% of patients.

The investigators concluded: “First-line durvalumab plus platinum/etoposide showed sustained overall survival improvement vs platinum/etoposide, but the addition of tremelimumab to durvalumab plus platinum/etoposide did not significantly improve outcomes vs platinum/etoposide. These results support the use of durvalumab plus platinum/etoposide as a new standard of care for the first-line treatment of extensive-stage SCLC.”

Luis Paz-Ares, MD, of the Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by AstraZeneca. For full disclosures of the study authors, visit thelancet.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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