Dato-DXd Shows Favorable Benefit in EGFR-Mutant NSCLC

Commentary
Video

A combined cohort composed of patients from the TROPION-Lung01 and TROPION-Lung-05 trials showed a survival advantage with dato-DXd vs docetaxel.

In an interview with CancerNetwork®, Jacob Sands, MD, assistant professor of Medicine at Harvard Medical School, thoracic oncologist at the Dana-Farber Cancer Institute, and investigator of the phase 2 TROPION-Lung05 trial (NCT04484142), which supported the accelerated approval of datopotamab deruxtecan-dlnk(dato-DXd; Datroway) in pretreated EGFR-mutant metastatic NSCLC in June 2025, outlined prior efficacy data that the agent displayed in this patient population.1,2

He initially outlined the phase 3 TROPION-Lung01 trial (NCT04656652), which evaluated second-line dato-DXd vs docetaxel in patients who previously received EGFR tyrosine kinase inhibitors (TKIs) and platinum-based chemotherapy. Sands explained that all-comers were included on the trial; those with actionable genomic alterations saw the greatest overall survival (OS) benefit, with EGFR mutations representing the most common actionable genomic alterations.

Furthermore, Sands highlighted results from the TROPION-Lung05 trial, which was a single-arm trial that exclusively enrolled patients with actionable genomic alterations. Expressing that EGFR mutations were also expressed in a majority of patients in this trial, he suggested that these patients experienced the greatest benefit from dato-DXd.

He concluded by highlighting combined data from the EGFR-mutated disease cohorts of both trials, which the FDA used to support the approval of dato-DXd in EGFR-mutant metastatic NSCLC. He highlighed a median PFS of 5.8 months and a median OS of 15.6 months, which he expressed was favorable compared with docetaxel.

Transcript

[Dato-DXd] is another treatment option for patients [and] a new one as well. Patients who have [received] prior EGFR TKI and prior chemotherapy, the standard of care, are then looking at next-line docetaxel. We have a randomized trial of dato-DXd vs docetaxel in all comers [for NSCLC]. [A total of] 17% of patients that enrolled to that trial had tumors with actionable genomic alterations, and that is where we saw the greatest benefit.

To speak broadly about TROPION-Lung01, beyond just actionable genomic alterations, in the squamous cohort, we saw that it underperformed [vs] docetaxel. In the nonsquamous cohort, we saw statistically significant improvement in [PFS]; we saw a trend of improvement in [OS] that matches the PFS benefit but did not reach statistical significance, meaning that the confidence interval crossed 1. In that 17% group of those with actionable genomic alterations, that OS trend was much bigger. Amongst those in the actionable genomic alteration cohort, the EGFR-mutated [subgroup] represented the majority of those alteration groups in that subset.

TROPION-Lung05 was a study that was similar. It was a single-arm trial, but patients who had previously [received] targeted therapy and platinum-based chemotherapy then ended up [receiving] dato-DXd. Only [patients with] tumors with actionable genomic alterations [were] enrolled. Again, the piece of the pie that was the biggest was the one of EGFR-mutated [disease], and EGFR-mutated did look better than the [ALK-rearranged subgroup] as well.

I know the focus is really the EGFR group, per the recent FDA approval. We now we have a cohort of essentially combining all EGFR [mutant subgroups] from TROPION-Lung01 as well as TROPION-Lung05, and within that, we see a median [PFS] benefit of 5.8 months and a median [OS] of 15.6 months. As far as how it compares to docetaxel, I’d say it compares favorably.

References

  1. Sands J, Ahn MJ, Lisberg A, et al. Datopotamab deruxtecan in advanced or metastatic non-small cell lung cancer with actionable genomic alterations: results from the phase II TROPION-Lung05 study. J Clin Oncol. Published online January 6, 2025. doi:10.1200/JCO-24-01349
  2. FDA grants accelerated approval to datopotamab deruxtecan-dlnk for EGFR-mutated non-small cell lung cancer. News release. FDA. June 23, 2025. Accessed July 28, 2025. https://tinyurl.com/mtay7ab9
  3. Ahn MJ, Tanaka K, Paz-Ares L, et al. Datopotamab deruxtecan versus docetaxel for previously treated advanced or metastatic non-small cell lung cancer: the randomized, open-label phase III TROPION-Lung01 study. J Clin Oncol. Published online September 9, 2024. doi:10.1200/JCO-24-01544
Recent Videos
The National ICE-T Conference may inspire future collaboration between community and academic oncologists in the management of different cancers.
4 experts in this video
Osimertinib/chemotherapy and amivantamab/lazertinib have exhibited an efficacy advantage vs osimertinib in patients with EGFR-mutant NSCLC.
4 experts in this video
One of the largest obstacles to tackle in the kidney cancer landscape will be translating the research on rare kidney cancer subtypes into clinical trials.
Long-term toxicities like infections and secondary primary malignancies remain a concern when sequencing novel agents for those with multiple myeloma.
Zanzalitinib exhibited favorable data when evaluated alone or in combination with anti-PD-1 immune checkpoint inhibition in phase 1 RCC trials.
The investigational agent exhibited superior efficacy vs pembrolizumab in patients with lung cancer, suggesting potential efficacy in kidney cancer.
Management of adverse effects and access to cellular therapies among community oncologists represented key points of discussion in multiple myeloma.
Related Content