Dato-DXd Outperforms Docetaxel in Previously Treated, Advanced NSCLC

Datopotamab deruxtecan (Dato-DXd) can prolong progression-free survival (PFS), when compared to docetaxel, in patients with previously treated, advanced non-small lung cancer (NSCLC), according to phase 3 data presented at the ESMO Congress 2023. 

“Dato-DXd is the first antibody-drug conjugate to demonstrate a statistically significant improvement in progression-free survival over docetaxel in patients with previously treated, locally advanced or metastatic non-small lung cancer,” said study presenter Aaron Lisberg, MD, of the University of California, Los Angeles.

Dr Lisberg cautioned, however, that the PFS benefit was primarily driven by patients with non-squamous histology.

These results come from the TROPION-LUNG01 study (ClinicalTrials.gov Identifier: NCT04656652), which enrolled patients with stage IIIB-IV NSCLC who were docetaxel-naïve. Patients without actionable genomic alterations had to have received 1-2 prior lines of therapy, including platinum-based chemotherapy and anti-PD-(L)1 therapy.

Patients with actionable genomic alterations were eligible if they were positive for EGFR, ALK, NTRK, BRAF, ROS1, MET exon 14 skipping, or RET mutations. They also had to have received 1-2 prior approved targeted therapies, platinum-based chemotherapy, and 1 or fewer anti-PD-(L)1 therapies.

A total of 604 patients were randomly assigned to receive Dato-DXd at 6 mg/kg every 3 weeks (n=299) or docetaxel at 75 mg/m² every 3 weeks (n=305). Baseline characteristics were generally well balanced between the arms.

The median treatment duration was 4.2 months with Dato-DXd and 2.8 months with docetaxel. The median follow-up was 13.1 months in the Dato-DXd arm and 13.0 months in the docetaxel arm.

The median PFS was 4.4 months in the Dato-DXd arm and 3.7 months in the docetaxel arm (hazard ratio [HR], 0.75; 95% CI, 0.62-0.91; P =.004). The 6-month PFS rate was 40.8% in the Dato-DXd arm and 28.2% in the docetaxel arm. The 9-month PFS rate was 30.1% and 17.8%, respectively.

“This improvement in progression-free survival in the Dato-DXd-treated patients is supported by a more than doubling of the objective response rate … and a longer duration of response,” Dr Lisberg said.

The objective response rate was 26.4% with Dato-DXd and 12.8% with docetaxel. The median duration of response was 7.1 months and 5.6 months, respectively.

Dr Lisberg and colleagues also assessed PFS by histology and found that Dato-DXd was  only associated with improved PFS in patients with non-squamous NSCLC.

In patients with non-squamous NSCLC, the median PFS was 5.6 months with Dato-DXd and 3.7 months with docetaxel (HR, 0.63; 95% CI, 0.51-0.78). In patients with squamous NSCLC, the median PFS was 2.8 months with Dato-DXd and 3.9 months with docetaxel (HR, 1.38; 95% CI, 0.94-2.02).

In the overall cohort, overall survival (OS) was not significantly different between the treatment arms. The median OS was 12.4 months with Dato-DXd and 11.0 months with docetaxel (HR, 0.90; 95% CI, 0.72-1.13).

The rate of treatment-related adverse events (TRAEs) was 87% in both arms. The rate of grade 3 or higher TRAEs was 25% in the Dato-DXd arm and 41% in the docetaxel arm.

There were 3 fatal TRAEs in the Dato-DXd arm (2 cases of interstitial lung disease/pneumonitis and 1 case of sepsis). There were 2 fatal TRAEs in the docetaxel arm (a case of interstitial lung disease/pneumonitis and a case of septic shock).

The most common TRAEs in the Dato-DXd arm were stomatitis (47%), nausea (34%), and alopecia (32%). The most common TRAEs in the docetaxel arm were alopecia (35%), neutropenia (26%), and anemia (20%).

Based on these results, Dr Lisberg concluded that “Dato-DXd is a potential new, meaningful therapy for patients with previously treated, non-squamous non-small lung cancer.”

Disclosures: This research was supported by Daiichi Sankyo. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Ahn M-J, Lisberg A, Paz-Ares L, et al. Datopotamab deruxtecan (Dato-DXd) vs docetaxel in previously treated advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC): Results of the randomized phase III study TROPION-Lung01. Presented at ESMO Congress 2023. Oct. 20-24, 2023. Madrid, Spain. Abstract LBA12.

This article originally appeared on Cancer Therapy Advisor