The final overall survival (OS) data from the TROPION-Lung01 trial indicated a small numerical advantage for datopotamab deruxtecan (Dato-DXd) compared to docetaxel in patients with advanced non-small cell lung cancer (NSCLC) receiving second-line treatment. The OS was 13 months for Dato-DXd, compared to 12 months for docetaxel, with a hazard ratio (HR) of 0.95 (95% confidence interval [CI] between 0.78 and 1.14).
In the non-squamous cohort, the OS was more pronounced, but still non-significant, with 15 months for Dato-DXd versus 12 months for docetaxel, yielding an HR of 0.84 (95% CI 0.68-1.05).
“TROPION-Lung01, when looking specifically at the non-squamous cohort, showed improvement in progression-free survival, an improvement in overall response rate, an improvement in the median duration of response, a favorable toxicity profile, and now, an overall survival advantage that is numerical, which supports the use of Dato-DXd as a potential new therapeutic option for patients with previously treated non-squamous, non-small cell lung cancer eligible for subsequent therapy,” said Jacob Sands, MD, Oncology Medical Director at the International Patient Center of Dana-Farber Cancer Institute and Assistant Professor of Medicine at Harvard Medical School.
Dr. Sands presented the final results of TROPION-Lung01 during a session titled The New Generation of Cytotoxics at the 2024 World Conference on Lung Cancer.
Earlier data indicated a statistically significant improvement in progression-free survival (PFS) for Dato-DXd, with an HR of 0.75 (95% CI between 0.82 and 0.91, p = 0.004) compared to docetaxel. PFS was improved in the non-squamous arm, with an HR of 0.63 (95% CI between 0.51 and 0.79). OS data included 11 months of follow-up to the prior PFS report.
The dual primary endpoints for the trial were OS and PFS. Secondary endpoints included overall response rate (ORR), duration of response (DOR), and safety.
“Survival outcomes for patients with advanced NSCLC receiving docetaxel-based regimens in the second-line setting and beyond have remained poor,” Dr. Sands said. “Multiple trials of novel regimens have failed in this setting. TROPION-Lung01, as previously reported, met its dual primary endpoint of progression-free survival in favor of Dato-DXd.”
The randomized, open-label, phase III trial enrolled 299 patients with stage IIIB, IIIC, or IV to Dato-DXd and 305 patients to receive docetaxel. Patients without actionable genomic alterations had received one or two lines of prior therapy, which included platinum-based chemotherapy and anti-PD-(L)1 therapy. Those with actionable alterations, such as EGFR, ALK, NTRK, BRAF, ROS1, MET exon 14 skipping, or RET, had undergone one or two approved prior lines of therapy in addition to platinum-based chemotherapy and/or anti-PD-(L)1 therapy.
The overall safety profile was consistent with earlier reports with no late-onset toxicities noted, Dr. Sands said. Dato-DXd exhibited fewer treatment-related adverse events (TRAEs) classified as grade 3 or higher compared to docetaxel, as well as a lower incidence of TRAEs leading to dose reductions (20% versus 30%) or treatment discontinuations (8% versus 12%). The median DOR for Dato-DXd was 4 months, while for docetaxel, it was 3 months. Stomatitis was the most common TRAE associated with Dato-DXd, occurring in 47% of patients, primarily classified as grade 1 (23%) or grade 2 (18%). Hematologic toxicities, including neutropenia and febrile neutropenia, were more prevalent with docetaxel, reported at 26% compared to 5% and 16% compared to 3%, respectively. There were no new drug-related interstitial lung disease events or deaths since the PFS data lock in 2023.
