Adding novel agents to durvalumab-based regimens has shown promising results in both resectable non-small cell lung cancer (NSCLC) and high-risk hormone receptor (HR)-positive breast cancer. Two recent trials, NeoCOAST-2 in NSCLC and Neo-CheckRay in breast cancer, highlight the potential of these combinations to improve pathologic response rates. These findings were presented at the International Association for the Study of Lung Cancer (IASLC) 2024 World Conference on Lung Cancer and the European Society for Medical Oncology (ESMO) Congress 2024, respectively.
Enhanced Responses in Resectable NSCLC with Datopotamab Deruxtecan
The phase II NeoCOAST-2 trial evaluated the efficacy and tolerability of novel perioperative treatment combinations in patients with resectable NSCLC. Patients were randomized to receive neoadjuvant durvalumab plus platinum-doublet chemotherapy with either oleclumab, monalizumab, or datopotamab deruxtecan (Dato-DXd). The Dato-DXd arm also included single-agent platinum chemotherapy.
Results indicated that the combination of Dato-DXd, durvalumab, and single-agent platinum chemotherapy yielded the highest pathologic complete response rate at 34.1%, compared to 20.0% with oleclumab and 26.7% with monalizumab. The major pathologic response rates were 65.9%, 45.0%, and 53.3%, respectively. These response rates are notably higher than the 17.2% pathologic complete response rate observed in the phase III AEGEAN trial with perioperative durvalumab plus chemotherapy.
"This is the first global phase II study showing encouraging pathologic response rates for Dato-DXd in the neoadjuvant setting for patients with resectable NSCLC," said Tina Cascone, MD, PhD, of The University of Texas MD Anderson Cancer Center. She also noted that the combination demonstrated a manageable safety profile, with similar rates of adverse events compared to historical Dato-DXd monotherapy data.
Durvalumab Improves Outcomes in High-Risk Breast Cancer
In the Neo-CheckRay trial, adding durvalumab, with or without oleclumab, to neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT) significantly improved pathologic complete response rates in patients with high-risk HR-positive breast cancer. The study focused on the luminal B subtype, a subgroup known to benefit from chemotherapy but with pathologic complete response rates of only about 15% with chemotherapy alone.
The trial's results showed a doubling of pathologic complete response rates from 16.7% with standard care (chemotherapy + SBRT) to 33.3% with durvalumab and 31.1% with durvalumab plus oleclumab. Alex De Caluwé, MD, a radiation oncologist at Institut Jules Bordet in Belgium, noted particularly encouraging results with the addition of immunotherapy in PD-L1-negative and node-positive subgroups.
"Neo-CheckRay is the first phase II trial to examine the addition of immune checkpoint inhibitors and the anti-CD73 oleclumab to neoadjuvant chemotherapy and SBRT in luminal B breast cancer," Dr. De Caluwé stated. The novel treatment combination was overall safe and feasible, with a manageable increase in grade 3 and 4 adverse events in the immunotherapy arms.
Implications and Future Directions
Both the NeoCOAST-2 and Neo-CheckRay trials suggest that combining durvalumab with novel agents can enhance treatment efficacy in NSCLC and high-risk breast cancer, respectively. While these phase II trials provide encouraging signals, larger, randomized controlled trials are needed to confirm these findings and assess long-term outcomes. Further research is also warranted to identify predictive biomarkers and optimize treatment strategies for specific patient subgroups.
