The European Commission has approved two new cancer treatments: enfortumab vedotin in combination with pembrolizumab for urothelial cancer and amivantamab-vmjw in combination with chemotherapy for non-small cell lung cancer (NSCLC). These approvals mark significant advancements in first-line treatment options for patients with specific forms of these aggressive cancers.
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Enfortumab Vedotin and Pembrolizumab for Urothelial Cancer
Enfortumab vedotin combined with pembrolizumab has been approved for adult patients with unresectable or metastatic urothelial cancer who are eligible for platinum-containing chemotherapy. This decision is supported by findings from the phase 3 EV-302/KEYNOTE-A39 trial, which demonstrated that the combination significantly improved patient outcomes compared to standard chemotherapy.
In the trial, the combination therapy led to a median overall survival (OS) of 31.5 months, compared to 16.1 months with chemotherapy, representing a 53% reduction in the risk of death. Additionally, patients experienced a median progression-free survival (PFS) of 12.5 months versus 6.3 months with chemotherapy, reducing the risk of disease progression or death by 55%.
The objective response rate (ORR) for the combination was 67.7%, with a complete response rate of 29.1%, compared to an ORR of 44.4% and a complete response rate of 12.5% with chemotherapy. The combination also demonstrated a favorable safety profile, with grade 3 or higher treatment-related adverse effects (AEs) occurring in 55.9% of patients receiving the combination therapy versus 69.5% in the chemotherapy arm.
The most common grade 3 or higher AEs associated with enfortumab vedotin and pembrolizumab included maculopapular rash, hyperglycemia, neutropenia, peripheral sensory neuropathy, diarrhea, and anemia. Despite these adverse effects, the combination’s overall benefit in extending survival and delaying disease progression makes it a valuable treatment option for eligible patients.
Amivantamab-vmjw with Chemotherapy for NSCLC
The European Commission has also approved amivantamab-vmjw in combination with carboplatin and pemetrexed for the treatment of patients with locally advanced or metastatic NSCLC who have EGFR exon 19 deletions or exon 21 L858R substitution mutations. This approval is based on results from the phase 3 MARIPOSA-2 study, which showed that the combination therapy significantly improved progression-free survival (PFS) and intracranial PFS compared to chemotherapy alone.
Patients treated with amivantamab-vmjw and chemotherapy achieved a median PFS of 6.3 months, compared to 4.2 months with chemotherapy alone. The combination also reduced the risk of intracranial progression or death by 45%, with a median intracranial PFS of 12.5 months versus 8.3 months.
The safety profile of amivantamab-vmjw combined with chemotherapy was consistent with that of the individual agents. However, 72% of patients experienced grade 3 or higher adverse effects, compared to 48% in the chemotherapy-only group. The most common grade 3 or higher AEs included neutropenia, thrombocytopenia, anemia, and leukopenia. Additionally, 58% of patients in the amivantamab-vmjw arm experienced any-grade infusion-related reactions, and serious treatment-emergent AEs occurred in 32% of these patients, compared to 20% in the chemotherapy group. Notably, grade 3 or 4 bleeding events were observed in 1% of patients receiving the combination therapy.
References
- “European Commission Approves Astellas’ PADCEVTM (enfortumab vedotin) in Combination with KEYTRUDA® (pembrolizumab) for First-Line Treatment of Advanced Urothelial Cancer,” Aug. 28, 2024. https://www.astellas.com/en/news/29371
- T. B. Powles et al., “LBA6 EV-302/KEYNOTE-A39: Open-label, randomized phase III study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (Chemo) in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC),” Annals of Oncology, vol. 34, p. S1340, Oct. 2023, doi: 10.1016/j.annonc.2023.10.106.
- “European Commission approves RYBREVANT®▼ (amivantamab) in combination with chemotherapy for the treatment of adult patients with advanced EGFR-mutated non-small cell lung cancer after failure of prior therapy,” JNJ.com, Aug. 27, 2024. https://www.jnj.com/media-center/press-releases/european-commission-approves-rybrevant-amivantamab-in-combination-with-chemotherapy-for-the-treatment-of-adult-patients-with-advanced-egfr-mutated-non-small-cell-lung-cancer-after-failure-of-prior-therapy
- A. Passaro et al., “Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study,” Annals of Oncology, vol. 35, no. 1, pp. 77–90, Jan. 2024, doi: 10.1016/j.annonc.2023.10.117.
Viktor Grünwald
