FDA Approves Generic Pemetrexed for Nonsquamous NSCLC

The FDA has approved a generic form of pemetrexed for intravenous administration as a single-agent in patients with locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) that has not progressed following 4 cycles of first-line platinum-based chemotherapy.¹

The injection was also approved for use as a single agent in the treatment of patients with recurrent, metastatic nonsquamous NSCLC who received previous treatment with chemotherapy. The generic is a salt form version of the reference product Alimta, which was developed by Eli Lilly.

Pemetrexed was first approved on February 4, 2004, for use in combination with cisplatin in the treatment of patients with malignant pleural mesothelioma. In a phase 3 trial, a total of 456 patients were randomized to receive pemetrexed and cisplatin (n = 226) or cisplatin alone (n = 222).²

Results showed that the median survival in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months with cisplatin alone (HR, 0.77; P = .020, two-sided long-rank test). Moreover, the combination was found to significantly prolong the median time to progression compared with the monotherapy, at 5.7 months versus 3.9 months, respectively (P = .001). Response rates in the investigational and control arms were 41.3% and 16.7%, respectively (P < .0001).

With regard to safety, the agent was found to cause myelosuppression. The most commonly experienced adverse effects (AEs) included neutropenia, fatigue, leukopenia, nausea, dyspnea, and vomiting.

The recommended dose of pemetrexed is 500 mg/m2 given as an intravenous infusion over 10 minutes on day 1 of each 21-day treatment cycles in combination with cisplatin at a dose of 75 mg/m2 infused over the course of 2 hours starting 30 minutes following treatment with pemetrexed.

Patients need to receive oral folic acid and vitamin B(12) injections before the start of treatment and they must continue to receive these injections during treatment with pemetrexed to decrease severe AEs. Patients should also be given corticosteroids with chemotherapy to decrease the likelihood of skin rashes.

The regulatory decision was based primarily on the superior survival seen with pemetrexed in combination with cisplatin.

More recently, in February 2020, the FDA granted a final approval to pemetrexed for injection (Pemfexy) as an alternative to standard pemetrexed for use in patients with locally advanced or metastatic nonsquamous NSCLC and for those with malignant pleural mesothelioma.

Specifically, the indication is for use in combination with cisplatin in patients with locally advanced or metastatic nonsquamous NSCLC; locally advanced or metastatic nonsquamous NSCLC whose disease did not progress after 4 cycles of first-line platinum-based chemotherapy, as maintenance treatment; locally advanced or metastatic nonsquamous NSCLC following previous chemotherapy treatment as a single agent; and for those with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery in combination with cisplatin.³

References

1. Teva Pharmaceuticals unit Actavis Generics wins FDA approval for lung cancer drug pemetrexed. News release. Nasdaq. August 24, 2020. Accessed August 25, 2020. https://bit.ly/2Qp1gNN.
2. Hazarika M, White RM, Johnson JR, et al. FDA drug approval summaries: pemetrexed (Alimta). Oncologist. 2004;9(5):482-488. doi:10.1634/theoncologist.9-5-482
3. Eagle Pharmaceuticals receives final FDA approval for Pemfexy (pemetrexed for injection). News release. Eagle Pharmaceuticals. February 10, 2020. Accessed August 25, 2020. https://bit.ly/2SircfX.