Among patients with advanced or recurrent endometrial cancer (aEC), first-line treatment with Lenvima (lenvatinib) plus Keytruda (pembrolizumab) did not result in statistically significant improvements in survival and progression versus treatment with chemotherapy, researchers have reported.
Researchers published their findings from the phase 3 European Network of Gynecological Oncological Trial (ENGOT)-en9/LEAP-001 study in the Journal of Clinical Oncology.
The Food and Drug Administration (FDA) previously granted the combination regular approval for patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation in 2021 based on the Study 309/KEYNOTE-775 trial following an accelerated approval that was granted in 2019.
Glossary
Mismatch repair deficient: Mismatch repair deficiency, according to the National Cancer Institute, describes cells that have mutations in genes that are involved in correcting mistakes made when DNA is copied, and mismatch repair deficient cells usually have many DNA mutations, which may lead to cancer.
Mismatch repair proficient: When the body’s DNA repair system functions as it should.
Progression-free survival: the time a patient lives without their disease spreading or worsening.
Overall survival: the time a patient lives, regardless of disease status.
Neoadjuvant: treatment that occurs before the main treatment, such as surgery.
Adjuvant: treatment that occurs after the main treatment.
Cerebrovascular accident: a stroke.
Intracranial hematoma: collection of blood inside the skull.
Pneumonitis: inflammation of the lungs.
Subcutaneous hemorrhage: bleeding under the skin.
“Negative trials are important and may inform practice as much as positive trials. Paclitaxel-carboplatin–containing regimens are standard-of-care initial treatment for advanced endometrial cancer. The [Lenvima plus Keytruda] combination is an effective option in patients with progression on or after previous chemotherapy,” noted Journal of Clinical Oncology senior deputy editor Dr. Kathy D. Miller in a contextual supplement published with the study.
Researchers enrolled 842 patients with stage 3 to 4 or recurrent endometrial cancer with no previous chemotherapy or disease progression at least six months after neoadjuvant/adjuvant platinum-based chemotherapy, with 420 patients in the Lenvima and Keytruda arm, including 320 in the pMMR population, and 422 patients in the chemotherapy arm, including 322 in the pMMR population.
As of the final analysis data cutoff of Oct. 2, 2023, the median progression-free survival was 9.6 months among the Lenvima and Keytruda arm versus 10.2 months in the chemotherapy arm in the pMMR population and 12.5 months versus 10.2 months among all patients, according to the study’s findings.
Median overall survival was 30.9 months for the Lenvima plus Keytruda arm and 29.4 months in the chemotherapy arm for pMMR patients, and 37.7 months versus 32.1 months for all patients, researchers reported.
Regarding safety, researchers reported that no new safety signals were identified with either treatment regimen in the trial. For patients who received at least one dose of treatment, 98% of patients on the combination arm and 97% on the chemotherapy arm experienced treatment-related side effects of any grade. Notably, grade 3 (severe) to 4 (life-threatening) treatment-related side effects occurring in 76% and 66% of patients, respectively.
Notably, 2% of participants in the Lenvima plus Keytruda arm and than 1% of those on the chemotherapy arm died due to treatment-related side effects, researchers reported. The causes of death for the Lenvima plus Keytruda group were listed as cerebrovascular accident (two patients), large intestine perforation, death (general disorder), cerebral hemorrhage, hemorrhagic stroke, intracranial hematoma, acute respiratory failure, pneumonitis and subcutaneous hemorrhage (one each); and for the chemotherapy group, it was listed as pneumonia aspiration and sepsis (one each).
“This phase 3 trial of [Lenvima plus Keytruda] versus paclitaxel-carboplatin [chemotherapy] did not meet the prespecified statistical criteria for [progression-free survival] or [overall survival] as first-line treatment for patients with [mismatch repair-proficient (pMMR)] aEC. … Our findings underscore the challenges of replacing rather than adding to the entrenched standard of care, paclitaxel-carboplatin, in aEC in the first-line setting,” researchers concluded.
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Reference
“First-Line Lenvatinib Plus Pembrolizumab Versus Chemotherapy for Advanced Endometrial Cancer: A Randomized, Open-Label, Phase III Trial” by Dr. Christian Marth et al., Journal of Clinical Oncology.
