Dato-DXd Falls Short in Overall NSCLC Population, Shows Benefit in Non-Squamous Disease

Dato-DXd did not improve survival outcomes when compared with docetaxel chemotherapy.

Dato-DXd (datopotamab deruxtecan) did not significantly improve survival compared with docetaxel in patients with pretreated locally advanced or metastatic non-small cell lung cancer (NSCLC), according to topline data from the phase 3 TROPION-Lung01 clinical trial.

These preliminary findings were announced by AstraZeneca and Daiichi Sankyo, the co-manufacturers of the drug.

The pharmaceutical companies did not give specific data regarding overall survival (OS; time patients live until death of any cause) in TROPION-Lung01. A press release from Daiichi-Sankyo mentioned that although OS was numerically higher in the Dato-DXd group, there was no statistically significant difference between the two drugs in the overall study population. This means that there was not a big enough difference between the two OS outcomes for researchers to say with confidence that one treatment regimen outperformed the other.

Dato-DXd is an antibody-drug conjugate, which is a type of drug that works by targeting and binding to a specific protein on cancer cells — in this case, TROP2. Once the medication is connected to the cancer cell, it then releases a “payload” of a cancer-killing drug.

While Dato-DXd did not improve OS in the overall study population, data presented at the 2023 European Society for Medical Oncology Congress did show that the drug improved progression-free survival (PFS; time patients live without disease worsening) compared with docetaxel.

Data showed that Dato-DXd reduced the risk of disease progression or death by 25% in the overall study population. The median PFS was 4.4 months for patients in the Dato-DXd group and 3.7 months in the docetaxel group. Patients were also more likely to respond to the antibody-drug conjugate, with objective response rates (ORR; percentage of patients whose disease shrinks or disappears after treatment) of 24.6% and 12.8% in the Dato-DXd and docetaxel groups, respectively.

Benefits Observed in Non-Squamous NSCLC

Of note, the findings showed that there was a statistically significant OS difference between Dato-DXd and docetaxel observed in patients with non-squamous NSCLC. According to the American Cancer Society, squamous cell carcinoma is a type of lung cancer that starts in the flat cells that line the airways of the lungs. Non-squamous disease occurs elsewhere in the lungs.

This group of patients also had more marked improvements in PFS, as presented at the 2023 European Society for Medical Oncology Congress. More specifically, in patients with non-squamous NSCLC, Dato-DXd reduced the risk of disease progression or death by 37% compared to docetaxel. Median PFS was 5.6 months compared to 3.7 months in the Dato-DXd and docetaxel groups, respectively, and the ORR was 31.2% versus 12.8%. Four patients with non-squamous NSCLC in the Dato-DXd group experienced a complete response, meaning that all signs of cancer disappeared, compared to no patients in the docetaxel group.

"The improvement in overall survival seen with [Dato-DXd] coupled with the previously reported clinically meaningful progression-free survival, more than doubling of overall response and prolonged duration of response compared to docetaxel suggest that this TROP2-directed antibody-drug conjugate could potentially become an important new treatment for patients with non-squamous non-small cell lung cancer in this advanced metastatic setting,” said Dr. Ken Takeshita, global head, R&D, Daiichi Sankyo, in the press release.

Based on these findings, the Food and Drug Administration (FDA) granted a Biologics License Application (meaning that the agency is considering the drug for potential approval) to Dato-DXd for the treatment of adults with locally advanced or metastatic non-squamous NSCLC that received prior systemic therapy.

READ MORE: Dato-DXd to Be Reviewed by FDA for Metastatic Lung Cancer Treatment

“[Dato-DXd] is the only investigational therapy to show a clinically meaningful survival improvement in patients with previously treated non-squamous non-small cell lung cancer versus docetaxel, which has long been unsurpassed in this post-targeted treatment and post-immunotherapy setting,” said Dr. Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, said in the release.

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