Dr Cascone on Evaluating Neoadjuvant Durvalumab-Based Regimens in Resectable NSCLC

“Nearly all [patients] across the 3 arms started neoadjuvant treatment and the vast majority completed 4 treatment cycles.”

Tina Cascone, MD, PhD, associate professor, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses findings from the phase 2 NeoCOAST-2 trial (NCT05061550) evaluating the safety and efficacy of perioperative treatment with durvalumab in combination with oleclumab, monalizumab, or AZD0171 plus platinum-doublet chemotherapy; volrustomig or rilvegostomig plus platinum-doublet chemotherapy; or datopotamab deruxtecan (Dato-DXd) in combination with durvalumab or rilvegostomig plus single-agent platinum chemotherapy in patients with resectable, early-stage non–small cell lung cancer (NSCLC).

This analysis included 202 patients randomized across 3 treatment arms. In arm 1, patients received neoadjuvant oleclumab plus durvalumab and platinum-doublet chemotherapy (n = 60); in arm 2, patients received monalizumab plus durvalumab and platinum-doublet chemotherapy (n = 60); and in arm 4, patients were treated with Dato-DXd plus durvalumab and single-agent platinum chemotherapy (n = 44). The majority of patients across all arms (72%-76%) completed 4 treatment cycles.

Surgical outcomes demonstrated high resection rates, with 92.2%, 92.1% and 95.8% of patients undergoing surgery in arms 1,2 and 4, respectively. R0 resection rates ranging from 90% to 96% across all 3 arms. Additionally, 74% to 83% of patients completed surgery-initiated adjuvant therapy. Pathologic complete response (pCR) rates were 20.0% in arm 1, 26.7% in arm 2, and 34.1% in arm 4. Major pathologic response (mPR) rates were observed in 45.0%, 53.3%, and 65.9% of patients in arms 1, 2, and 4, respectively.

The highest pCR and mPR rates were achieved in arm 4 with Dato-DXd plus durvalumab and platinum-based chemotherapy. Additionally, pCR rates were higher across all arms in patients with a PD-L1 tumor proportion score (TPS) of 50% or greater compared with those with lower PD-L1 expression. Among patients in arm 1, pCR rates were 32.0% in those with TPS of at least 50% (n = 25), compared with 17.6% in those with TPS less than 1% (n = 17). Similar trends were observed in patients with TPS of at least 50% in arms 2 (n = 20) and 4 (n = 17), with pCR rates of 35.0% and 41.2%, respectively.

The safety profiles of all treatment arms were manageable, with comparable rates of adverse effects vs currently approved neoadjuvant regimens. These findings suggest that incorporating novel anticancer agents in the neoadjuvant setting alongside durvalumab leads to high resection rates and response rates. Cascone concludes that further investigation of durvalumab-based combinations in the neoadjuvant setting is warranted for patients with resectable NSCLC.