Rafal Tarnawski

Phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer: ENGOT-en9/LEAP-001

Pembrolizumab plus lenvatinib is a novel combination with promising efficacy in patients with advanced and recurrent endometrial cancer. This combination demonstrated high objective response rates in a single-arm phase 1b/2 trial of lenvatinib plus pembrolizumab in patients with advanced endometrial cancer (KEYNOTE-146/Study 111) after ≤2 previous lines of therapy. In a randomized phase 3 trial of lenvatinib in combination with pembrolizumab versus treatment of physician's choice in patients with advanced endometrial cancer (KEYNOTE-775/Study 309), after 1‒2 previous lines of therapy (including neoadjuvant/adjuvant), this combination improved objective response rates, progression-free survival, and overall survival compared with chemotherapy. To compare the efficacy and safety of first-line pembrolizumab plus lenvatinib versus paclitaxel plus carboplatin in patients with newly diagnosed stage III/IV or recurrent endometrial cancer, with measurable or radiographically apparent disease. Pembrolizumab plus lenvatinib is superior to chemotherapy with respect to progression-free survival and overall survival in patients with mismatch repair-proficient tumors and all patients (all-comers). Phase 3, randomized (1:1), open-label, active-controlled trial. Patients will receive pembrolizumab intravenously every 3 weeks plus lenvatinib orally daily or paclitaxel plus carboplatin intravenously every 3 weeks, stratified by mismatch repair status (proficient vs deficient). Patients with mismatch repair-proficient tumors will be further stratified by Eastern Cooperative Oncology Group performance status (0/1), measurable disease (yes/no), and prior chemotherapy and/or chemoradiation (yes/no). Adults with stage III/IV/recurrent histologically confirmed endometrial cancer that is measurable or radiographically apparent per blinded independent central review. Patients may have received previous chemotherapy only as neoadjuvant/adjuvant therapy and/or concurrently with radiation. Patients with carcinosarcoma (malignant mixed Müllerian tumor), endometrial leiomyosarcoma, or other high grade sarcomas, or endometrial stromal sarcomas were excluded. Progression-free and overall survival (dual primary endpoints). About 875 patients. Enrollment is expected to take approximately 24 months, with presentation of results in 2022. ClinicalTrials.gov, NCT03884101.

Global challenges of radiotherapy for the treatment of locally advanced cervical cancer

Cervical cancer represents a significant portion of the global cancer burden for women, with low- and middle-income countries carrying the bulk of this burden. Additionally, underserved populations in countries with sufficient resources may have a higher incidence of cervical cancer and poorer outcomes. Concurrent chemoradiotherapy is the standard-of-care treatment for locally advanced cervical cancer, which includes patients with stage IB3 to IVA disease, and it is effective for many patients; however, cervical cancer-related mortality remains high. The critical nature of cervical cancer treatment is underscored by the recent launch of the World Health Organization global initiative to accelerate the elimination of cervical cancer using a triple-intervention strategy of increased vaccination, screening, and treatment. The initiative calls for 90% of all patients diagnosed with cervical cancer to receive the appropriate treatment, but to reach this global goal there are significant barriers related to radiotherapy that must be addressed. We discuss and review evidence of the lack of adherence to guideline-recommended treatment, brachytherapy underutilization, limited access to radiotherapy in low- and middle-income countries, as well as regional limitations within high-income countries, as the major barriers to radiotherapy treatment for locally advanced cervical cancer. We further review ways these barriers are currently being addressed and, in some cases, make additional recommendations to address these issues. Finally, despite receiving recommended treatments, many patients with locally advanced cervical cancer have a poor prognosis. With effective administration of current standards of care, the global community will be able to shift focus to advancing treatment efficacy for these patients. We review several types of therapies under clinical investigation that are additions to concurrent chemoradiotherapy, including immune checkpoint inhibitors, antiangiogenic agents, DNA repair inhibitors, human papillomavirus vaccines, and radiosensitizing nanoparticles.

Revealing Engagement Patterns Among Endometrial Cancer Patients

The study intends to investigate the personal experiences of endometrial cancer patients who take part in a separate clinical study including a specific medication intervention. The major focus will be on closely following individuals' rates of trial completion and withdrawal. The data collected from this study will help improve future outcomes for all endometrial cancer patients as well as those in under-represented demographic groups.

Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Versus Chemotherapy for Endometrial Carcinoma (ENGOT-en9 / MK-7902-001)

The purpose of this study is to compare the efficacy of pembrolizumab + lenvatinib to chemotherapy in female participants with Stage III, IV, or recurrent endometrial carcinoma. It is hypothesized that the combination of pembrolizumab + lenvatinib will be superior to chemotherapy for progression-free survival (PFS) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR). It is also hypothesized that the combination of pembrolizumab + lenvatinib will be superior to chemotherapy for overall survival (OS). As of Amendment 7 eligible participants on study completion will be able to transition to an extension study, if available, in which they can continue to receive pembrolizumab monotherapy, lenvatinib monotherapy, or a combination of both pembrolizumab and lenvatinib as received in the parent study.