The Targeted Pulse: Drug Approvals & Cytoreductive Therapy's Vital Role

Dato-DXd Charges Forward with Acceptance of Application for Non-Small Cell Lung Cancer

The FDA accepted the biologics license application for the use of datopotamab deruxtecan (Dato-DXd) in previously treated, advanced, nonsquamous non-small cell lung cancer (NSCLC). The application acceptance is based on the data from the phase 3 TROPION-Lung01 trial (NCT04656652), which demonstrated superior progression-free survival (PFS) compared with the current standard-of-care treatment docetaxel.

“...Dato-DXd was a better tolerated drug from a global perspective, although there are some clear differences in terms of toxicity profile. It appears to be a potential new, meaningful therapy for patients with non-squamous metastatic advanced NSCLC eligible for second-line chemotherapy,” said Aaron Lisberg, MD, thoracic medical oncologist at the University of California, Los Angeles, in an interview with Targeted Oncology^TM.

Effective Results in EGFR-Mutant Lung Cancer Led to Osimertinib Plus Chemo Approval

With a 38% reduction in risk of disease progression or death, the combination of osimertinib (Tagrisso) and chemotherapy has been approved by the FDA for patients with locally advanced or metastatic EGFR-mutated NSCLC. The approval is based on the phase 3 FLAURA2 trial (NCT04035486), which yielded “exciting results,” said Joshua Sabari, assistant professor, Department of Medicine at NYU Grossman School of Medicine, and director of High Reliability Organization Initiatives at the Perlmutter Cancer Center.

“We saw a significant improvement in median PFS in that 25-to-26-month range for osimertinib plus chemotherapy vs osimertinib alone in that 16-to-17-month range,” he stated.

Newfound Relief for Advanced Melanoma Patients with Lifileucel Approval

Lifileucel (Amtagvi; LN-44) recently received FDA approval for the treatment of patients with advanced melanoma who experienced progression during or after anti-PD1/L1 therapy and/or targeted therapy. The approval of this agent is based on data from the phase 2 C-144-01 trial (NCT02360579) and brings hope for patients facing “…a life-threatening cancer that can cause devastating impacts to affected individuals, with a significant risk of metastasizing and spreading to other areas in the body,” said Nicole Verdun, MD, director of the Office of Therapeutic Products in CBER.

“The approval of Amtagvi represents the culmination of scientific and clinical research efforts leading to a novel T-cell immunotherapy for patients with limited treatment options,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research.

Essential Information on Cytoreduction Therapy in Myeloproliferative Neoplasms

Douglas Tremblay, MD, assistant professor of medicine and hematologist at the Icahn School of Medicine at Mount Sinai, expressed his views on cytoreduction therapy in myeloproliferative neoplasms (MPNs), stating, “I do not think there’s enough evidence to recommend one cytoreductive agent over the other, particularly hydroxyurea vs interferon-based therapies.”

He outlined the benefits, risks, and various considerations associated with cytoreduction therapy in MPNs, emphasizing the importance of cytoreductive therapy in mitigating thrombotic risk, specifically essential thrombocytopenia and polycythemia, in MPNs.

New Hope with Tepotinib Approval for Non-Small Cell Lung Cancer MET exon 14

Another FDA approval has been granted for NSCLC, this time for tepotinib (Tepmetko), indicated for the treatment of patients with NSCLC harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations. This agent received accelerated approval based on data from the phase 2, nonrandomized, multicohort, open-label VISION trial (NCT02864992), which demonstrated improved responses.

“These data are particularly meaningful for patients…who tend to be older and who are not, as a result, well-represented in the pivotal phase 3 studies that have cemented chemotherapy and immunotherapy as standards of care. Indeed, overall survival for our older patients can be as short as 8 to 10 months, as reported in recent prospective studies, and so a median OS of 20 months is encouraging to see, particularly as it’s maintained on longer follow-up,” said Paul K. Paik, MD, clinical director, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center.

Thank you for joining us for this week’s Targeted Pulse. Look out for more recaps to come.