On November 8, the FDA approved cemiplimab-rwlc (Libtayo) in combination with platinum-based chemotherapy for patients with advanced non-small cell lung cancer (NSCLC).1 The recommended dose is 350 mg intravenously (IV) over a 30-minute course every 3 weeks, and the agent comes in a single-dose vial. two
Patients receiving cemiplimab should not have EGFR, ALKeither ROS1 Aberrations must also not be eligible for surgery or definitive chemoradiation, or must have metastatic disease.
The approval was supported by data from trial 16113 (NCT03409614), which randomly assigned 466 previously untreated patients with 2:1 advanced NSCLC to receive immunochemotherapy or chemotherapy plus placebo. Overall survival (OS), progression-free survival (PFS), and overall response rates (ORR) represented the key outcomes. Median OS was 21.9 months (95% CI, 15.5; not evaluable) [NE]) with immunochemotherapy and 13.0 months (95% CI, 11.9-16.1) with chemotherapy plus placebo. Median PFS between the 2 cohorts was 8.2 months (95% CI, 6.4-9.3) and 5.0 months (95% CI, 4.3-6.2), respectively ( HR, 0.56, 95% CI, 0.44-0.70; P <.0001). The confirmed ORR was 43% (95% CI, 38%-49%) and 23% (95% CI, 16%-30%), respectively.
Study 16113 was a multicenter, multinational, double-blind, randomized, active controlled trial. PD-L1 status was not considered in the eligibility criteria; however, those with tumors harboring EGFR, ALK, or ROS1, patients requiring systemic immunosuppression, or patients with ongoing or recent autoimmune disease, were excluded from the investigation.
Patients randomized to the experimental arm received cemiplimab plus platinum-based chemotherapy every 3 weeks for 4 cycles followed by a combination of cemiplimab and maintenance chemotherapy. Control patients received platinum-based chemotherapy plus placebo every 3 weeks for cycles, followed by maintenance chemotherapy and placebo.
Chemotherapy consisted of any of the following combinations:
- Carboplatin area under the curve (AUC) of 5 or 6 plus paclitaxel at 200 mg/m2two
- Cisplatin at 75 mg/mtwo plus paclitaxel at 200 mg/m2two
- Carboplatin AUC of 5 or 6 plus pemetrexed at 500 mg/m2two
- Cisplatin at 75 mg/mtwo and pemetrexed at 500 mg/mtwo
In the trial, the most common adverse events (AEs) included alopecia, musculoskeletal pain, nausea, fatigue, peripheral neuropathy, and decreased appetite.
Patients receiving cemiplimab may be at risk for immune-mediated AEs, including pneumonitis, colitis, hepatitis, endocrinopathies, dermatological AEs, nephritis and renal dysfunction, or solid organ transplant rejection. Hepatic enzymes, creatinine, and thyroid function should be assessed initially and periodically during treatment.two Infusion-related reactions can also occur with treatment. In this case, the rate of infusion should be reduced, interrupted, or permanently discontinued, depending on severity.
In addition, patients who undergo allogeneic hematopoietic stem cell transplantation and PD-1/PD-L1 blocking antibodies are at risk of serious complications.
The prescription label does not offer a recommended dose reduction for cemiplimab. However, in general, grade 3 irAEs warrant treatment discontinuation and grade 4 irAEs warrant permanent discontinuation. Patients with recurrent grade 3 irAEs, or those who are unable to reduce their corticosteroid dose to 10 mg or less within 12 weeks of starting steroids, will generally need to discontinue treatment.
Cemiplimab injection is a clear to slightly opalescent, colorless to pale yellow solution that may contain trace amounts of translucent to white particles. It should be stored in a refrigerator in the original carton. Nurses should not freeze or shake the solution.
- FDA approves cemiplimab-rwlc in combination with platinum-based chemotherapy for non-small cell lung cancer. Press release. FDA. November 8, 2022. Retrieved November 9, 2022. http://bit.ly/3UlUpEh
- Libtáyo. Prescription information. Regeneron Pharmaceuticals, Inc.; 2022. Accessed November 9, 2022. https://bit.ly/3hvaSHL