ADRIATIC: durvalumab after chemoradiotherapy for limited-stage small-cell lung cancer
For small-cell lung cancer confined to the chest, adding two years of durvalumab after chemoradiotherapy extended median survival from under three years to over four and a half, the first advance in this setting in decades.
Double-blind, placebo-controlled phase 3 trial of 730 patients with limited-stage small-cell lung cancer who had not progressed after concurrent platinum-etoposide chemoradiotherapy, randomised to durvalumab, durvalumab plus tremelimumab, or placebo for up to 24 months. Primary endpoints were overall survival and PFS for durvalumab versus placebo.
Median overall survival was 55.9 vs 33.4 months (HR 0.73) and median PFS 16.6 vs 9.2 months (HR 0.76). It applied the PACIFIC consolidation model to small-cell lung cancer and became the new standard for limited-stage disease.
- Median overall survival 55.9 vs 33.4 months; HR 0.73 (98.321% CI 0.54-0.98); 36-month OS 56.5% vs 47.6%.
- Median PFS 16.6 vs 9.2 months; HR 0.76; 24-month PFS 46.2% vs 34.2%.
- Grade 3-4 adverse events 24.4% vs 24.2%; pneumonitis or radiation pneumonitis of any grade 38.2% vs 30.2%.
- Benefit was consistent regardless of whether prophylactic cranial irradiation had been given.
Patients with limited-stage small-cell lung cancer who complete chemoradiotherapy without progression should now be offered up to two years of durvalumab consolidation, which extends life by almost two years on average. This is the first survival improvement for limited-stage disease since twice-daily radiotherapy and prophylactic cranial irradiation, and small-cell lung cancer is no longer a disease where immunotherapy gives only marginal gains.
- The durvalumab plus tremelimumab arm has not shown clear additional benefit and its role is unclear.
- Radiotherapy schedules varied (once or twice daily) and prophylactic cranial irradiation was optional, adding heterogeneity.
- Only patients without progression after chemoradiotherapy were eligible, as in PACIFIC.
- No biomarker predicts benefit; PD-L1 is not useful in small-cell lung cancer.
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