The U.S. Food and Drug Administration (FDA) has recently expanded its indications and granted approvals for three drugs, offering new options for patients with various forms of cancer. The approved drugs—dostarlimab-gxly for endometrial cancer, afamitresgene autoleucel for synovial sarcoma, and vorasidenib for Grade 2 astrocytoma or oligodendroglioma—represent critical progress in oncology, delivering more effective and targeted therapies.
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Dostarlimab-Gxly Expanded for Endometrial Cancer Treatment
The FDA has expanded the use of dostarlimab-gxly in combination with chemotherapy for adult patients with primary, advanced or recurrent endometrial cancer (EC). Previously approved only for patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) EC, this expansion now includes a broader population, providing more women with an effective treatment option.
The approval is based on the results of the RUBY trial, a randomized, double-blind, placebo-controlled study involving 494 patients. The trial demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS) in patients treated with dostarlimab-gxly alongside carboplatin and paclitaxel, compared to those receiving a placebo. Specifically, the median OS in the overall population was 44.6 months in the dostarlimab-gxly arm, compared to 28.2 months in the placebo arm, with a hazard ratio of 0.69, indicating a 31% reduction in the risk of death.
Despite its benefits, the treatment is associated with common adverse reactions, such as anemia, fatigue, peripheral neuropathy, and increased creatinine levels. However, the potential for extended survival makes dostarlimab-gxly a promising option for patients with advanced or recurrent EC.
Afamitresgene Autoleucel for Synovial Sarcoma Patients
The FDA has also granted accelerated approval to afamitresgene autoleucel, a genetically modified autologous T cell immunotherapy for adults with unresectable or metastatic synovial sarcoma. This approval is specifically for patients who are HLA-A02:01P, -A02:02P, -A02:03P, or -A02:06P positive and whose tumors express the melanoma-associated antigen A4 (MAGE-A4).
The approval comes following the data from the SPEARHEAD-1 trial, which showed an overall response rate (ORR) of 43.2%, with a median duration of response (DOR) of 6 months. These results are particularly encouraging, given the limited treatment options available for synovial sarcoma.
This treatment also comes with it’s own adverse events such as cytokine release syndrome, fatigue, and various other side effects; however, the potential for a meaningful response offers hope to those with this challenging diagnosis.
Vorasidenib for Low-Grade Gliomas
Rounding out these significant approvals, the FDA has approved vorasidenib for patients 12 years and older with Grade 2 astrocytoma or oligodendroglioma who have susceptible IDH1 or IDH2 mutations. This is the first systemic therapy approved by the FDA for this patient population, marking a major milestone in the treatment of low-grade gliomas.
The efficacy of vorasidenib was demonstrated in the INDIGO trial, which enrolled 331 patients. The trial results showed that patients receiving vorasidenib had a significantly longer progression-free survival (PFS) compared to those on placebo, with a hazard ratio of 0.39. Moreover, the time to the next intervention was substantially longer in the vorasidenib arm, highlighting its potential to delay disease progression and the need for additional treatment.
While vorasidenib has been shown to be effective, it is not without risks. Common adverse reactions include fatigue, headaches, and seizures, with some patients experiencing elevated liver enzymes. Nonetheless, the benefits of prolonged disease control and improved quality of life make vorasidenib a valuable addition to the treatment landscape for patients with low-grade gliomas.
References:
- https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-endometrial-cancer-indication-dostarlimab-gxly-chemotherapy
- https://www.nejm.org/doi/full/10.1056/NEJMoa2216334
- https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-afamitresgene-autoleucel-unresectable-or-metastatic-synovial-sarcoma
- https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.11563
- https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vorasidenib-grade-2-astrocytoma-or-oligodendroglioma-susceptible-idh1-or-idh2-mutation
- https://www.nejm.org/doi/full/10.1056/NEJMoa2304194
FDA Approval
