Dr Marth on Frontline Lenvatinib Plus Pembrolizumab in Endometrial Cancer

Christian Marth, MD, PhD, head, professor, Department of Obstetrics and Gynecology, Innsbruck Medical University, discusses findings from the phase 3 ENGOT-En9/LEAP-001 trial of first-line lenvatinib (Lenvima) plus pembrolizumab (Keytruda) vs chemotherapy in patients with advanced or recurrent endometrial cancer.

According to data presented at the 2024 SGO Annual Meeting, in the comparison between the investigative and chemotherapy regimens, health-related quality of life (QOL) levels were similar across most QOL scales, with lenvatinib plus pembrolizumab showing superiority in managing neuropathy and alopecia. The safety profile of lenvatinib plus pembrolizumab remained manageable and consistent with previous findings with this combination. These findings solidify the feasibility of using lenvatinib plus pembrolizumab as a viable combination for treating patients with advanced or recurrent endometrial cancer.

However, the trial did not achieve its primary end points of progression-free survival (PFS) and overall survival (OS) in the mismatch repair–proficient (pMMR) population, Marth reports, adding that nevertheless, some significant observations are worth noting.

Primarily, within the mismatch repair–deficient (dMMR) patient subgroup, comprising approximately 25% of the study population, there emerged a noteworthy extension in both PFS and OS with lenvatinib plus pembrolizumab, Marth explains. This finding indicates a potential avenue for tailored interventions in patients with dMMR disease. Conversely, it was intriguing to observe that among patients who had previously received neoadjuvant or adjuvant chemotherapy, the combination appeared to generate a benefit, he expands. This phenomenon might be attributable to the potential induction of chemoresistance by prior chemotherapy regimens, Marth elucidates. Consequently, the combination therapy involving checkpoint inhibition and angiogenesis inhibition with pembrolizumab plus lenvatinib presents a promising therapeutic approach for patients with prior chemotherapy exposure, a finding that warrants further investigation and validation, he states.

Although the trial did not yield anticipated results, these nuanced observations provide valuable insights into potential patient stratification strategies and treatment modalities, Marth continues. Further exploration and refinement of these findings could lead to more personalized and effective interventions for patients, according to Marth. Thus, there remains optimism for advancing precision medicine approaches in the management of this challenging disease, he concludes.