Throughout August, the FDA approved drugs for the treatment of diseases including non-small cell lung cancer, cutaneous T-cell lymphoma, astrocytoma/oligodendroglioma, and endometrial cancer.
Throughout the month of August, several cancer therapies have been approved by the FDA for diseases including non-small cell lung cancer (NSCLC), cutaneous T-cell lymphoma, astrocytoma and oligodendroglioma, and endometrial cancer.
Here is a select list of oncology drugs that received FDA approval this past month.
First-Line Amivantamab Plus Lazertinib Receives FDA Approval for EGFR-Positive Advanced NSCLC
This drug combination has been approved for treating locally EGFR-positive advanced or metastatic NSCLC.1 In the MARIPOSA trial (NCT04487080), amivantamab (Rybrevant) plus lazertinib (Lazcluze) demonstrated superior efficacy compared to standard treatments.2 In particular, amivantamab plus lazertinib reduced the risk of progression or death by 30% compared with osimertinib (Tagrisso; HR, 0.70; 95% CI, 0.58-0.85; P < .001). Patients treated with the combination (n = 429) had a median progression-free survival (PFS) of 23.7 months compared with 16.6 months for those treated with osimertinib (n = 429).
Regarding safety, the most common adverse effects reported in at least 20% of patients treated with amivantamab/lazertinib were rash, nail toxicity, infusion-related reactions with amivantamab, musculoskeletal pain, edema, stomatitis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19 infection, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity.3
FDA Approves Denileukin Diftitox for Relapsed/Refractory Cutaneous T-Cell Lymphoma
The FDA approved denileukin diftitox-cxdl (Lymphir) for the treatment of patients with relapsed/refractory cutaneous T-cell lymphoma who received at least 1 prior systemic therapy.4 This approval marks the first indication for this novel immunotherapy and the only treatment for cutaneous T-cell lymphoma that targets the IL-2 receptor.
The FDA approval is based on findings from the phase 3 Pivotal Study 302 (NCT01871727). The objective response rate in this study was 36.2% (95% CI, 25.0-48.7), with a complete response rate of 8.7%. The median time to response with denileukin diftitox was 1.41 months, with approximately 70% of patients achieving a response to therapy after 1 to 2 cycles of the therapy. More than half of patients (52%) had a duration of response of at least 6 months. In addition, 84.4% of patients whose skin was evaluable during the study had a decrease in skin tumor burden, with 12.5% of patients achieving a complete clearing of skin disease.
The prescribing information for denileukin diftitox includes a boxed warning for capillary leak syndrome, and that patients should be monitored for signs and symptoms during treatment. The warning also notes that denileukin diftitox should be withheld until capillary leak syndrome resolves, or permanently discontinue the treatment based on severity.
FDA Approves Vorasidenib to Treat Grade 2 Astrocytoma, Oligodendroglioma With IDH1, IDH2 Mutations
Vorasidenib (Voranigo) has been approved by the FDA to treat adults and pediatric patients aged 12 years and older with grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation.5 This is the first systemic therapy approved for grade 2 astrocytoma or oligodendroglioma with an IDH1 or IDH2 mutation.
This approval was based on findings from the INDIGO trial (NCT04164901). The hazard ratio for PFS in patients treated with vorasidenib was 0.39 (95% CI, 0.27-0.56; P < .0001). The vorasidenib group did not meet the median time to next intervention compared with 17.8 months in the placebo group (HR = 0.26; 95% CI, 0.15-0.43; P < .0001).
The most common adverse reactions, occurring in at least 15% of patients, included headache, fatigue, musculoskeletal pain, COVID-19 infection, nausea, diarrhea, and seizure. The most common grade 3 or 4 laboratory abnormalities, observed in at least 2% of patients, included increased aspartate aminotransferase levels, increased alanine aminotransferase levels, decreased neutrophil levels, and increase in gamma-glutamyl transpeptidase levels.
Perioperative Durvalumab Receives FDA Approval for Resectable NSCLC
Durvalumab (Imfinzi), an immune checkpoint inhibitor, has been approved by the FDA for use with platinum-containing chemotherapy as neoadjuvant treatment, followed by durvalumab as adjuvant treatment post-surgery, in adults with resectable NSCLC and no known EGFR mutations or ALK rearrangements.6-8
The approval was based on data from the phase 3 AEGEAN trial (NCT03800134), which demonstrated a statistically significant and clinically meaningful reduction in the risk of recurrence, progression, or death with the chemoimmunotherapy regimen vs chemotherapy alone. The median event-free survival (EFS) was not reached (NR; 95% CI, 31.9-NR) with durvalumab vs 25.9 months (95% CI, 18.9-NR) with placebo (stratified HR, 0.68; 95% CI, 0.53-0.88; P = .004). The 12- and 24-month EFS rates with durvalumab were 73.4% (95% CI, 67.9%-78.1%) and 63.3% (95% CI, 56.1%-69.6%), respectively, vs 64.5% (95% CI, 58.8%-69.6%) and 52.4% (95% CI, 45.4%-59.0%) with placebo.
FDA Expands Approval of Dostarlimab for Advanced, Recurrent Endometrial Cancer
Dostarlimab (Jemperli), an immune checkpoint inhibitor, has had its approval expanded by the FDA to include the treatment of primary advanced or recurrent endometrial cancer.9
The expanded approval is supported by data from the phase 3 RUBY trial (NCT03981796), which showed that in the overall population, patients treated with dostarlimab plus chemotherapy experienced a statistically significant improvement in overall survival (OS) compared with those treated with placebo plus chemotherapy (HR, 0.69; 95% CI, 0.54-0.89; 1-sided P = .002).10 The median OS was 44.6 months (95% CI, 32.6–not reached) in the dostarlimab arm vs 28.2 months (95% CI, 22.1-35.6) in the placebo arm.
Regarding safety, the most common adverse effects reported in at least 20% of all patients in the dostarlimab arm included anemia, increased creatinine, peripheral neuropathy, decreased white blood cell count, fatigue, nausea, alopecia, low platelets, increased glucose, lymphopenia, neutropenia, liver function test abnormalities, arthralgia, rash, constipation, diarrhea, decreased albumin, abdominal pain, dyspnea, decreased appetite, increased amylase, urinary tract infection and vomiting.
References
Liso-Cel Shows Comparable Real-World Outcomes in Relapsed/Refractory LBCL
December 9th 2024Real-world treatment with liso-cel showed a broad spectrum of outcomes that were comparable to those in the pivotal TRANSFORM and PILOT trials in patients with relapsed/refractory large B-cell lymphoma.