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Pembrolizumab Plus Lenvatinib Combination Shows Mixed Results in Gastroesophageal Cancer
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Key Takeaways
- Pembrolizumab plus lenvatinib improved progression-free survival but not overall survival in HER2-negative gastroesophageal adenocarcinoma.
- Pembrolizumab, an anti-PD-1 therapy, enhances immune detection and response against tumor cells.
The trial meets one of the study’s dual primary endpoints of progression-free survival, but did not meet its other primary endpoint of overall survival.
New study findings from Merck announced results from the phase 3 LEAP-015 (NCT04662710) trial, assessing pembrolizumab (Keytruda; Merck) plus lenvatinib (Lenvima; Eisai and Merck) in combination with chemotherapy for the first-line treatment among individuals with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastroesophageal adenocarcinoma.1
The results demonstrated that pembrolizumab plus lenvatinib-based regimen met one of the study’s dual primary endpoints of progression-free survival (PFS) at an interim analysis, but did not meet its other primary end point of overall survival (OS) at the final analysis. The study authors noted that a full assessment of the data is ongoing.1
Unresectable or metastatic HER2- negative gastroesophageal adenocarcinoma refers to stomach cancer, which originates in the area where the esophagus meets the stomach and has spread to other parts of the body. The cancer cannot be surgically removed, and lacks the HER2 protein, limiting treatment options. This typically results in a poor prognosis and is often treated with a combination of chemotherapy and immunotherapy drugs, like pembrolizumab.2
As an anti-programmed death receptor-1 (PD-1) therapy, pembrolizumab increases the ability of the body’s immune system to help detect and fight tumor cells. The monoclonal antibody blocks the interaction between PD-1, PD-L1 and PD-L2, which activates T lymphocytes, according to study authors.1
Despite its rarity, gastroesophageal adenocarcinoma is potentially fatal and is the most common type of esophageal cancer.3 Following, the 5-year survival rate for both gastric and esophageal cancer is 7% at a distant stage and 6% in the advanced stage, respectively.1
“Locally advanced unresectable or metastatic gastroesophageal adenocarcinoma remains a challenging disease to treat and a leading cause of cancer death worldwide,” Gregory Lubiniecki, MD, vice president of global clinical development at Merck Research Laboratories, said in a news release. “These study results add to our understanding of this combination and will inform our future research as we strive to improve outcomes for more patients with cancer.”1
The randomized, open-label, phase 3 LEAP-015 clinical trial was conducted in 2 parts—part 1 assessed the safety and part 2 was the main study. A total of 880 individuals were included in part 2 and were randomly assigned to receive 400 mg of pembrolizumab intravenously every 6 weeks, plus 8 mg of oral lenvatinib everyday with chemotherapy (CAPOX or mFOLFOX6) in the induction phase; or 400 mg of pembrolizumab intravenously for 6 weeks, for less than or equal to 16 doses, plus 20 mg of oral lenvatinib, or chemotherapy, in the consolidation phase.1
The primary end points of OS and PFS were assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in patients whose tumors express PD-L1 (Combined Positive Score [CPS] ≥1) and in all patients, according to study authors. The secondary endpoint of overall response rate (ORR) and duration of response was also assessed using the same system.1
The results displayed that pembrolizumab plus lenvatinib demonstrated statistically significant improvement in PFS and ORR, compared to standard of care chemotherapy. However, the combination did not meet OS in the final analysis.1
“While the LEAP-015 trial did not show a statistically significant increase in overall survival, we were pleased to observe an improvement in progression-free survival and objective response rate for patients treated with KEYTRUDA plus LENVIMA in combination with chemotherapy. These results contribute to the scientific community’s collective understanding of these complex diseases and add to the body of knowledge in oncology research. We are deeply grateful to the patients, caregivers and investigators who participated in this study.” Corina Dutcus, MD, senior vice president and oncology global clinical development lead at Eisai Inc, said in a news release.1
REFERENCES
1. Merck and Eisai Provide Update on Phase 3 LEAP-015 Trial Evaluating KEYTRUDA® (pembrolizumab) Plus LENVIMA® (lenvatinib) in Combination with Chemotherapy in Patients with Certain Types of Gastroesophageal Adenocarcinoma. Merck. News release. January 24, 2025. Accessed January 28, 2025. https://www.merck.com/news/merck-and-eisai-provide-update-on-phase-3-leap-015-trial-evaluating-keytruda-pembrolizumab-plus-lenvima-lenvatinib-in-combination-with-chemotherapy-in-patients-with-certain-types-of-ga/
2. FDA approves pembrolizumab with chemotherapy for HER2-negative gastric or gastroesophageal junction adenocarcinoma. FDA. November 16, 2023. Accessed January 28, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-chemotherapy-her2-negative-gastric-or-gastroesophageal-junction#:~:text=On%20November%2016%2C%202023%2C%20the%20Food%20and,HER2%2Dnegative%20gastric%20or%20gastroesophageal%20junction%20(GEJ)%20adenocarcinoma
3. Gastroesophageal Junction Adenocarcinoma: Is There an Optimal Management? ASCO Publications. News release. May 17, 2019. Accessed January 28, 2025. https://ascopubs.org/doi/10.1200/EDBK_236827
