PACIFIC Trials, DUART Trial, COAST Trial, and ADRIATIC Trial
Panelists discuss how adjuvant durvalumab after chemoradiotherapy (PACIFIC trial) established the standard of care for locally advanced non–small cell lung cancer, while the DUART trial showed potential benefits even in frail patients treated with radiation alone, the COAST trial demonstrated improved outcomes by adding trebananib to durvalumab, and the ADRIATIC trial revealed significant survival benefits from adjuvant durvalumab in limited-stage small cell lung cancer.
PACIFIC Trials, DUART Trial, COAST Trial, and ADRIATIC Trial
The PACIFIC trial established durvalumab as the standard of care for locally advanced non–small cell lung cancer following chemoradiotherapy, representing one of the most successful recent trials in thoracic oncology. Related studies, including PACIFIC-R, PACIFIC-2, and PACIFIC-6, explored variations of this approach with mixed results. Notably, PACIFIC-2, which administered durvalumab concurrently with chemoradiotherapy rather than sequentially, showed no benefit, leaving the original PACIFIC regimen as standard. The DUART trial investigated durvalumab in frail patients who received radiation without chemotherapy, demonstrating that some patients achieved long-term survival despite modest radiation doses when combined with effective systemic therapy.
The COAST trial was a phase 2 randomized study comparing durvalumab alone vs durvalumab plus oleclumab or durvalumab plus monalizumab following curative-intent chemoradiotherapy. Results showed improved outcomes with the addition of second immunomodulatory agents without significant increases in adverse events, particularly high-grade toxicities. This promising data has generated ongoing follow-up studies investigating combination immunotherapy approaches.
For limited-stage small cell lung cancer, the ADRIATIC trial demonstrated significant benefits with adjuvant durvalumab following chemoradiotherapy. The trial showed a 25% risk reduction for both progression-free and overall survival, with approximately 10% absolute benefit at multiple time points. Importantly, earlier initiation of immunotherapy after completing chemoradiotherapy correlated with greater benefit, mirroring findings from the PACIFIC trial. Safety profiles across these trials consistently showed no significant new toxicity signals when adding immunotherapy to radiotherapy, though pneumonitis rates increased modestly. Prior prophylactic cranial irradiation and radiation schedules did not significantly impact treatment benefits.
