- Immunotherapy can benefit some patients with extensive-stage small cell lung cancer (ES-SCLC), but existing biomarkers do not identify these individuals.
Why this matters
- New first-line treatments for ES-SCLC are urgently needed to improve on the limited efficacy seen with chemotherapy.
- Treating all patients is expensive in relation to the benefits gained, and exposes patients to unnecessary toxicity.
- Two new analyses confirmed that a minority of patients with ES-SCLC derive clinically relevant benefit from immunotherapy, but showed that existing biomarkers are not predictive of response.
- The CASPIAN study has previously shown that addition of durvalumab to standard etoposide+cisplatin (EP) chemotherapy in first-line treatment has a modest survival benefit, increasing median OS from 10.3 to 13.0 months (HR 0.73, 95% CI 0.591-0.909, P=0.0047). However, new data presented at ESMO 2019 showed that PD-L1 expression was low and had no significant effect on clinical outcomes.
- Patients treated with durvalumab had longer times to deterioration of symptoms, functioning, and health-related quality of life, as would be expected from the efficacy data.
- Atezolizumab added to EP was associated with median OS of 12.3 months in updated results from the IMPower-133 study after 22.9 months of follow-up (HR 0.76, 95% CI 0.60-0.95). Survival at 18 months was 34% with atezolizumab+EP compared with 21% with EP alone.
- Neither PD-L1 nor TMB biomarkers were predictive of benefit.
- "The two studies are similar in population, outcomes, and adverse events," said Dr Johan F. Vansteenkiste (University Hospital Leuven, Belgium), the invited discussant. While they represent the first progress in the treatment of ES-SCLC for decades, the results are clinically modest. He pointed to a recent economic analysis showing a very high cost-to-benefit ratio in treating unselected ES-SCLC patients with immunotherapy. However, biomarkers may be difficult to find in SCLC because of the limited amount of microenvironment tissue in the tumour.