Dato-DXd Improves Overall Survival Vs Chemo in Advanced Nonsquamous NSCLC

The FDA previously accepted a biologics license application for dato-DXd as a treatment for adult patients with previously treated advanced nonsquamous NSCLC in February 2024.

Treatment with datopotamab deruxtecan (dato-DXd) conferred an overall survival (OS) improvement vs docetaxel in patients with previously treated locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC), according to a press release on findings from the phase 3 TROPION-Lung01 trial (NCT04656652).¹

Although dato-DXd yielded a numerical OS improvement compared with docetaxel across the trial’s overall population, investigators noted that this outcome did not reach statistical significance. Specifically, dato-DXd produced a clinically meaningful OS improvement among a prespecified subgroup of patients with nonsquamous histology.

The safety profile of dato-DXd in the TROPION-Lung01 trial was comparable with prior reports of the agent. Additionally, the incidence of dose reductions or treatment discontinuation following adverse effects (AEs) was reduced with dato-DXd compared with docetaxel, and no instances of interstitial lung disease were adjudicated as being associated with the agent. Overall, investigators highlighted no new safety signals.

“Datopotamab deruxtecan is the only investigational therapy to show a clinically meaningful survival improvement in patients with previously treated nonsquamous [NSCLC] vs docetaxel, which has long been unsurpassed in this post-targeted treatment and post-immunotherapy setting,” Susan Galbraith, executive vice president of Oncology Research & Development at AstraZeneca, said in the press release.¹ “These results reinforce the potential for datopotamab deruxtecan to replace conventional chemotherapy in this late-line setting and underscore our confidence in ongoing trials evaluating this therapy in first-line lung cancer.”

Previously, dato-DXd was shown to have a progression-free survival (PFS) benefit compared with chemotherapy in the TROPION-Lung01 trial.² According to findings presented at the 2023 European Society for Medical Oncology Congress (ESMO), the median PFS across the overall population was 4.4 months in those who received dato-DXd vs 3.7 months in patients who received docetaxel (HR, 0.75; 95% CI, 0.62-0.91; P = .004). Additionally, the confirmed objective response rate (ORR) was 26.4% vs 12.8% in each respective arm.

The median PFS among patients with nonsquamous histology was 5.6 months in the dato-DXd arm and 3.7 months in the docetaxel arm (HR, 0.63; 95% CI, 0.51-0.78). Data also highlighted a confirmed ORR of 31.2% vs 12.8% in each respective arm across this subgroup.

“For patients with advanced non–small cell lung cancer, current standard of care second-line docetaxel is associated with limited benefit and substantial toxicity,” trial investigator Aaron Lisberg, MD, a thoracic medical oncologist at the University of California, Los Angeles Health, said in a press release on the PFS findings.² “The improvement in [PFS] observed with [dato-DXd], particularly in patients with non-squamous tumors, and the improved tolerability of this antibody drug conjugate compared to docetaxel, represent a meaningful advance for patients with lung cancer.”

Investigators plan to present additional data from the TROPION-Lung01 trial at a future medical meeting.

In the international, multicenter, open-label TROPION-Lung01 trial, approximately 600 adults with locally advanced or metastatic NSCLC were assigned to receive dato-DXd at 6.0 mg/kg or docetaxel at 75 mg/m². Investigators assessed patients at sites across Asia, Europe, North America, and South America.

The trial’s dual primary end points were PFS per blinded independent central review and OS. The trial’s secondary end points included ORR, duration of response, time to response, and disease control rate.

The FDA previously accepted a biologics license application for dato-DXd as a treatment for adult patients with previously treated advanced nonsquamous NSCLC in February 2024.³ Additionally, the European Medicines Agency validated a marketing application for dato-DXd in the same population in March 2024.⁴ Both applications were supported by findings from the TROPION-Lung01 trial.

References

1. Datopotamab deruxtecan showed clinically meaningful overall survival improvement vs. chemotherapy in patients with advanced nonsquamous non-small cell lung cancer in TROPION-Lung01 phase III trial. News release. AstraZeneca. May 27, 2024. Accessed May 28, 2024. https://tinyurl.com/9ax4ecn6
2. Datopotamab deruxtecan improved progression-free survival vs. chemotherapy in patients with previously treated non-small cell lung cancer in TROPION-Lung01 phase III trial. News release. AstraZeneca. October 23, 2023. Accessed May 28, 2024. https://tinyurl.com/5fpdwm99
3. Datopotamab deruxtecan biologics license application accepted in the US for patients with previously treated advanced nonsquamous non-small cell lung cancer. News release. AstraZeneca. February 19, 2024. Accessed May 28, 2024. http://tinyurl.com/2v5k3yhc
4. Two datopotamab deruxtecan applications validated in the EU for patients with advanced nonsquamous non-small cell lung cancer or HR-positive, HER2-negative breast cancer. News release. AstraZeneca. March 4, 2024. Accessed March 4, 2024. https://tinyurl.com/3va3hp8n