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Durvalumab Alone or Combined With Novel Agents for Unresectable Stage III Non Small Cell Lung Cancer Update From the COAST Randomized Clinical Trial summary
This episode reviews the COAST trial, which evaluated durvalumab alone or in combination with two novel immunomodulators—oleclumab (anti-CD73) and monalizumab (anti-NKG2A)—as consolidation therapy after platinum-based concurrent chemoradiotherapy in unresectable stage III NSCLC. In this phase 2, open-label, randomized study (n=186), patients with ECOG 0–1 were assigned to durvalumab alone, durvalumab plus oleclumab, or durvalumab plus monalizumab for up to 12 months. The primary endpoint was confirmed objective response rate; secondary endpoints included progression-free survival, overall survival, and safety. Results showed higher objective response rates with the combinations (durvalumab alone 23.9%; with oleclumab 35.0%; with monalizumab 40.3%), and significant improvements in progression-free survival for both combination arms (hazard ratios ~0.59 and ~0.63, respectively) compared with durvalumab alone. No OS improvement was observed yet, consistent with the phase 2 design and limited follow-up. Safety profiles were similar across arms, with immune-related events aligning with known durvalumab toxicities and no major increases in toxicity from adding oleclumab or monalizumab. Mechanistically, oleclumab reduces adenosine-mediated immunosuppression by blocking CD73, while monalizumab relieves NKG2A-mediated inhibition of NK and CD8+ T cells, theoretically enhancing PD-L1 blockade efficacy. Clinicians should note the selective eligibility (post-cCRT, ECOG 0–1) and ongoing need for phase 3 confirmation (PACIFIC-9) to determine OS benefit and potential shifts in standard of care. Practical takeaways include vigilant monitoring for immune-related adverse events, adherence to durvalumab consolidation, and awareness of potential overlapping toxicities. The COAST data are encouraging but require further validation before changing practice.
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By Pharmacy & Acute Care UniversityThis episode reviews the COAST trial, which evaluated durvalumab alone or in combination with two novel immunomodulators—oleclumab (anti-CD73) and monalizumab (anti-NKG2A)—as consolidation therapy after platinum-based concurrent chemoradiotherapy in unresectable stage III NSCLC. In this phase 2, open-label, randomized study (n=186), patients with ECOG 0–1 were assigned to durvalumab alone, durvalumab plus oleclumab, or durvalumab plus monalizumab for up to 12 months. The primary endpoint was confirmed objective response rate; secondary endpoints included progression-free survival, overall survival, and safety. Results showed higher objective response rates with the combinations (durvalumab alone 23.9%; with oleclumab 35.0%; with monalizumab 40.3%), and significant improvements in progression-free survival for both combination arms (hazard ratios ~0.59 and ~0.63, respectively) compared with durvalumab alone. No OS improvement was observed yet, consistent with the phase 2 design and limited follow-up. Safety profiles were similar across arms, with immune-related events aligning with known durvalumab toxicities and no major increases in toxicity from adding oleclumab or monalizumab. Mechanistically, oleclumab reduces adenosine-mediated immunosuppression by blocking CD73, while monalizumab relieves NKG2A-mediated inhibition of NK and CD8+ T cells, theoretically enhancing PD-L1 blockade efficacy. Clinicians should note the selective eligibility (post-cCRT, ECOG 0–1) and ongoing need for phase 3 confirmation (PACIFIC-9) to determine OS benefit and potential shifts in standard of care. Practical takeaways include vigilant monitoring for immune-related adverse events, adherence to durvalumab consolidation, and awareness of potential overlapping toxicities. The COAST data are encouraging but require further validation before changing practice.