Pembrolizumab Shows Promise in NSCLC, Breast Cancer

An analysis of pembrolizumab (Keytruda; Merck) has confirmed that it offers a promising option for patients with various forms of lung and breast cancers, according to a poster presented at the American Society of Health-System Pharmacists (ASHP) 2022 Midyear Clinical Meeting.

Lung cancer is the second most common cancer in men and women, and non­–small cell lung cancer (NSCLC) represents 84% of total cases. On the other hand, triple-negative breast cancer (TNBC) is a rare form of the disease representing 15% of invasive breast cancer cases.

Pembrolizumab is an immune checkpoint inhibitor approved in multiple cancers and being investigated in many others. It works by stopping the connection between programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) to prevent replication. In combination with chemotherapy, it is a first-line treatment for squamous NSCLC and metastatic NSCLC for patients with PD-L1 greater than 50% and is indicated for patients with locally recurrent unresectable or metastatic TNBC with tumors expressing PD-L1.

To investigate data in both indications, Amanda Liu, a student from the St. John’s University College of Pharmacy and Health Sciences, conducted PubMed literature searches to find the most relevant information evaluating pembrolizumab’s efficacy in TNBC and NSCLC during preliminary phase 1b and phase 3 studies, respectively. A statistical analysis from these studies compared the efficacy of pembrolizumab against both diseases.

The double-blinded KEYNOTE-407 phase 3 trial investigated pembrolizumab plus chemotherapy in 559 patients with squamous NSCLC who were between 29 and 88 years of age. Patients were included if they had squamous NSCLC, had received no previous therapy for metastatic disease, more than 1 measurable lesion, and had no central nervous system metastases.

Additionally, the KEYNOTE-189 trial investigated pembrolizumab plus chemotherapy in patients with metastatic NSCLC, with 616 participants between the ages of 34 and 84 years. Patients in this trial were included if they had metastatic NSCLC without mutations, no previous therapy for metastatic disease, more than 1 measurable lesion, and no central nervous system metastases.

Both trials evaluated overall survival (OS) and progression-free survival (PFS), with secondary endpoints of response rate, duration of response (DoR), and safety. At 12 months, the OS rate in the KEYNOTE-407 trial was 65.2% in the treatment arm compared with 48.3% in the control arm. Similarly, PFS was 6.4 months and 4.8 months, respectively.

Safety data found that 69.8% of patients in the treatment arm experienced grade 3 or higher adverse events (AEs), compared with 68.2% of patients in the control arm. Finally, the DoR was 7.7 months in the treatment arm versus 4.8 months in the control arm.

The KETNOTE-189 trial found similar results, with an OS rate of 69.2% versus 49.4% at 12 months in the treatment arm and control arm, respectively. PFS was 8.8 months versus 4.9 months in the treatment arm and control arm, respectively, and 67.2% of patients in the treatment arm experienced grade 3 or higher AEs compared with 49.4% of patients in the control arm. The DoR was 11.2 months in the treatment arm versus 7.8 months in the control arm.

Taken together, these results suggest that pembrolizumab is highly effective in both squamous and metastatic NSCLC.

“Compared with placebo, Keytruda showed a greater effectiveness and…a better life expectancy for patients with either squamous NSCLC or metastatic NSCLC,” Amanda Liu said in an interview with Pharmacy Times.

The KEYNOTE-012 and KEYNOTE-173 trials were examined to establish efficacy and safety of pembrolizumab in TNBC. The KEYNOTE-012 trial was a phase 1b trial among participants between 29 and 72 years of age who were diagnosed with estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who had received no previous therapy for metastatic disease. It also included PD-L1-positive tumors. Primary endpoints were overall response rate (ORR) with complete response or partial response, and secondary endpoints were PFS, DoR, and OS.

The KEYNOTE-173 trial included patients with ER- negative, PR- negative, HER2-negative, previously untreated, high-risk, early-stage, non-metastatic TNBC. Primary endpoints were safety and recommended phase 2 dose, with secondary endpoints of pathological complete response (pCR) rate, ORR, event-free survival, and OS.

Results from the KEYNOTE-012 trial found an ORR of 18.5%, PFS of 1.9 months, and 15% of patients experienced grade 3 or higher AEs. OS in this trial was 11.2 months.

The KEYNOTE-189 trial found a pCR of 60% and 73% of patients experienced grade 3 or higher neutropenia, with 10% experiencing other AEs at grade 3 or higher. The OS was 98% at 12 months in patients who received platinum-containing chemotherapy and in 80% of patients who did not.

Based on this comparison, Liu concluded that pembrolizumab is a favorable immunotherapy for patients with certain forms of lung and breast cancers. In patients with metastatic NSCLC, the addition of pembrolizumab to chemotherapy resulted in longer survival and PFS than chemotherapy alone. Additionally, when used with chemotherapy, pembrolizumab provides a synergistic response to increase survival rates.

“As you can see from the data, it really shows Keytruda to be a promising candidate in the different types of cancers in the lung—NSCLC, and in TNBC,” Liu said.

REFERENCE

Liu A. Comparing the Effectiveness of Keytruda Against Non–Small Cell Lung Cancer and Triple-Negative Breast Cancer. Poster. Presented at American Society of Health-System Pharmacists (ASHP) 2022 Midyear Clinical Meeting. December 5, 2022.