FDA Expands Alimta Label With Keytruda, Chemo Combo for Frontline NSCLC Treatment
The approval is based on data demonstrating improved progression-free survival and overall survival in patients with metastatic nonsquamous non-small cell lung cancer.
Officials with the FDA have expanded the label of pemetrexed for injection (Alimta, Eli Lilly) in combination with pembrolizumab (Keytruda, Merck) and platinum chemotherapy, according to a press release.
With this approval, pemetrexed plus pembrolizumab is indicated for use along with platinum chemotherapy for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC) with no EGFR or ALK genomic tumor aberrations.
Pemetrexed in combination with pembrolizumab and carboplatin was previously approved under the FDA’s accelerated approval process, with full approval contingent upon data demonstrating clinical benefit, according to Eli Lilly.
The approval of the new indication is based on results from Merck’s phase 3 KEYNOTE-189 trial. The study evaluated pemetrexed in combination with pembrolizumab and cisplatin or carboplatin compared with pemetrexed in combination with placebo and cisplatin or carboplatin in 616 untreated patients with metastatic nonsqumaous NSCLC, regardless of PD-L1 expression.
Patients were randomized into 2 treatment groups:
- Pemetrexed (500 mg/m2) with vitamin supplementation plus pembrolizumab (200-mg fixed dose every 3 weeks) plus cisplatin (75 mg/2) or carboplatin AUC 5 mg/mL/min on day 1 every 3 weeks (Q3W) for 4 cycles, followed by pemetrexed 200 mg Q3W, or
- Pemetrexed (500 mg/m2) with vitamin supplementation plus saline placebo and cisplatin (75 mg/m2) or carboplatin AUC 5 mg/mL/min Q3W for 4 cycles, followed by pemetrexed (500 mg/m2) plus placebo Q3W.
The pemetrexed plus pembrolizumab group demonstrated a progression-free survival of a median of 8.8 months compared with 4.9 months in the group that received the placebo. Additionally, the overall response rate in the pemetrexed plus pembrolizumab arm was 48% compared with 19% in the pemetrexed plus placebo arm.
In August 2018, pembrolizumab was approved for use in combination with chemotherapy for this indication, as well.
“KEYNOTE-189 demonstrated an exceptional effect of the Alimta-pembrolizumab-platinum chemotherapy combination in the first-line setting, offering significantly improved survival in patients with metastatic nonsqumaous non-small cell lung cancer with no EGFR or ALK genomic tumor aberrations,” Anne White, president of Lilly Oncology, said in a statement. “This new indication reinforces Lilly’s continued commitment to providing practice-changing treatment options that can make a meaningful difference for people living with lung cancer.”
Safety was evaluated in 405 patients who received pemetrexed in combination with pembrolizumab and platinum chemotherapy and 202 patients who received placebo, pemetrexed, and platinum chemotherapy. Adverse reactions occurring in ³20% of patients receiving pemetrexed in combination with pembrolizumab and platinum chemotherapy were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).
FDA Expands Lilly’s Alimta (pemetrexed) Label with Combination of Keytruda (pembrolizumab) and Platinum Chemotherapy for the First-Line Treatmnt of Metastatic Nonsquamous Non-Small Cell Lung Cancer [news release]. Eli Lilly. https://investor.lilly.com/news-releases/news-release-details/fda-expands-lillys-alimtar-pemetrexed-label-combination. Accessed January 31, 2019.