FDA Approves Generic IV Pemetrexed in Advanced or Metastatic Nonsquamous NSCLC

The FDA has granted approval to a generic form of the chemotherapy agent pemetrexed, which is indicated for intravenous administration in patients with locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) that have not progressed following 4 cycles of first-line platinum-based chemotherapy.¹

This news follows a prior approval for injectable pemetrexed as treatment of patients with locally advanced or metastatic nonsquamous NSCLC that have not progressed after 4 cycles of first-line platinum-based chemotherapy.² In addition, the injectable pemetrexed agent was FDA approved for the treatment of patients with recurrent, nonsquamous NSCLC who received prior chemotherapy.

Pemetrexed has been a part of the treatment landscape for lung disease for years after the non-generic form of the drug was first granted FDA approval in 2004 as treatment of malignant pleural mesothelioma, based on results from a phase 3 clinical trial of pemetrexed plus cisplatin versus cisplatin alone in 465 patients.³

In total, 226 patients were randomized to the pemetrexed arm and 222 were enrolled in the cisplatin monotherapy arm. The population was compiled of mostly male patients who were a median of 61 years (range, 29-85) in the combination arm and 60 years (range, 19-84 years) in the cisplatin arm. The majority of the patient population identified as Caucasian, including 90.3% of the pemetrexed combination arm and 92.8% of the cisplatin arm. In addition, most patients were stage IV at baseline with epithelial histology. Baseline performance scores were 90-100 in 51.8% of patients in the pemetrexed arm and 56.3% of the cisplatin arm.

Pemetrexed was administered at a dose of 500 mg/m2 and diluted with saline 100 ml. Cisplatin was dosed at 75 mg/m2 and administered via infusion over a period of 2 hours. The primary end point being explored in the study was survival.

Treatment with the pemetrexed combination led to a median survival of 12.1 months compared with 9.3 months among patients who received cisplatin alone (HR, 0.77; 95% CI, 0.61-0.96; 2-sided log-rank P =.020). Progression-free survival was also a significant improvement with pemetrexed plus cisplatin compared with cisplatin alone (P =.001). Overall, in the pemetrexed combination arm versus the control arm, responses were observed in 41.3% and 16.7% of patients, respectively.

The safety analysis included patients who had received a folic acid vitamin B12 supplement. A total of 168 of this subgroup was from the pemetrexed/cisplatin arm and 163 patients were from the cisplatin alone arm. The group was predominantly male, Caucasian, and had good performance statuses. The median age of the subgroup was 61 years (range, 19-85 years).

In terms of safety, the most common adverse events observed were neutropenia, fatigue, leukopenia, nausea, dyspnea, and vomiting. Pemetrexed was also found to cause myelosuppression in patients.

_References:

_{1. Teva Pharmaceuticals Unit actavis generics wins fda approval for lung cancer drug pemetrexed. News release. Nasdaq. August 24, 2020. Accessed August 26, 2020. https://bit.ly/32uX4BB}

_{2. 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.}

_{3. 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