Updated Results of the CASPIAN Trial in SCLC From ESMO 2021

John V. Heymach, MD, PhD, reviews updated results from the phase III CASPIAN trial for patients with extensive-stage SCLC (small cell lung cancer) as presented at ESMO 2021.

John V. Heymach, MD, PhD: This year at ESMO Congress 2021, we also saw an update on the CASPIAN study, presented by Dr Luis Paz-Ares. Just as a reminder, CASPIAN was the phase III trial testing durvalumab plus etoposide and EP [platinum chemotherapy] for 4 cycles, or durvalumab/tremelimumab plus EP as compared to EP alone. The initial analysis did show an overall survival benefit for the durvalumab plus EP arm. At the initial analysis, the hazard ratio for overall survival benefit was 0.73. The durvalumab plus tremelimumab arm did not actually show an overall survival benefit at that initial analysis. Here at ESMO, Dr Paz-Ares presented the 3-year updated survival. It was encouraging to see that, not only were the benefits sustained, but actually grew relative to the initial report. That's encouraging to see because often we see overall survival advantages shrink over time as curves converge, but here the benefit has grown. We now have a 3-year, 36-month update for the primary arm — the durvalumab plus EP arm — which is now considered 1 of the standards of care in the US. The hazard ratio has actually been reduced from 0.73 down to 0.71. Really encouragingly, if you look at the percentage of patients who are still alive at 3 years, it's almost tripled in the durvalumab arm at 17.6%, and in the control arm it's 5.8%, so about a 12% difference. That's really encouraging; that's a significant step forward, because we see that overall survival benefit really is persisting, and I think for the first time we see that long-term survival growing for patients with extensive-stage small-cell lung cancer.

Obviously, we would like long-term survival to be better than the 18% we're seeing now at 3 years, but that really is a marked advance as compared to the 5.8% we were seeing before. I thought it was also interesting that the durvalumab/tremelimumab arm is also improving over time in terms of the hazard ratio. The hazard ratio now is 0.81, and the nominal P-value is 0.02, so it is statistically significant, but it's not better than the durvalumab plus EP arm, so the addition of tremelimumab here doesn't look like it's adding appreciable benefit. I think overall the results here are encouraging. We see that the benefits are sustained, that there is long-term benefit for the addition of durvalumab to etoposide and platinum. I think this really supports — and in many ways, cements — first-line immunotherapy as being an important addition to chemotherapy for extensive-stage small-cell lung cancer.

Transcript Edited for Clarity

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