Researchers have demonstrated that the combination of durvalumab with the TROP2-directed antibody-drug conjugate datopotamab deruxtecan may yield high pathologic complete response rates in patients with resectable non–small cell lung cancer (NSCLC), according to findings presented by Cascone et al at the International Association for the Study of Lung Cancer (IASLC) 2024 World Conference on Lung Cancer (Abstract PL02.07).
Study Methods and Results
The open-label, multicenter phase II NeoCOAST-2 trial built on the results of the NeoCOAST and AEGEAN studies as foundation for evaluating the efficacy of durvalumab in combination with chemotherapy and novel agents as neoadjuvant therapy, followed by adjuvant therapy with durvalumab alone or combined with additional agents.
In this study, researchers randomly assigned 202 patients with untreated, histologically confirmed stage IIA to IIIB NSCLC—stratified by PD-L1 expression—to receive neoadjuvant durvalumab and platinum-doublet chemotherapy with oleclumab (arm 1, n = 76), neoadjuvant durvalumab and platinum-doublet chemotherapy with monalizumab (arm 2, n = 72), or neoadjuvant durvalumab and single-agent platinum chemotherapy with datopotamab deruxtecan (arm 4, n = 54). They sought to improve pathologic complete response rates in patients with resectable NSCLC.
The patients received neoadjuvant therapy every 3 weeks for four cycles prior to surgery, followed by adjuvant treatment with the respective regimens until disease progression or up to 1 year. The primary endpoints of the trial included pathologic complete response rate, safety, and tolerability. The secondary endpoints were event-free survival, feasibility of surgery, major pathologic response rate, and objective response rate.
The researchers noted that 92.2%, 92.1%, and 95.8% of the patients in arms 1, 2, and 4, respectively, underwent surgery. The pathologic complete response rates were 20% in arm 1, 26.7% in arm 2, and 34.1% in arm 4, with corresponding major pathologic response rates of 45%, 53.3%, and 65.9%, respectively. The patients in arm 4 showed the highest pathologic complete response rate and a generally favorable safety profile.
Treatment-related adverse events occurred in 94.6% of patients in arm 1, 90.1% of those in arm 2, and 96.3% of those in arm 4—with grade ≥ 3 treatment-related adverse events reported at 31.1%, 29.6%, and 18.5%, respectively.
Conclusions
“The findings highlight the potential of combining durvalumab with novel anticancer agents to build on what we have learned in the perioperative immunotherapy arena for patients with early-stage, resectable NSCLC to enhance treatment outcomes and safety profiles,” emphasized lead study author Tina Cascone, MD, PhD, of The University of Texas MD Anderson Cancer Center. “The NeoCOAST-2 study is the first global phase II platform trial to provide evidence that the combination of durvalumab with novel agents, particularly [datopotamab deruxtecan], yields the highest rates of pathologic complete response among the tested regimens. This promising efficacy, coupled with a manageable safety profile, underscores the potential of these novel treatment combinations in improving outcomes for patients with resectable NSCLC, and the results affirm the viability of integrating novel anticancer agents into neoadjuvant and perioperative therapy for enhanced clinical benefit,” she concluded.
Disclosure: For full disclosures of the study authors, visit cattendee.abstractsonline.com.
