Lenvatinib Plus Pembrolizumab Versus Standard of Care for Previously Treated Metastatic Colorectal Cancer: Final Analysis of the Randomized, Open-Label, Phase III LEAP-017 Study.

PURPOSE: Treatment options are limited for patients with previously treated metastatic colorectal cancer (mCRC). In the LEAP-017 study, we evaluate whether lenvatinib in combination with pembrolizumab improves outcomes compared with standard of care (SOC) in previously treated mismatch repair proficient or not microsatellite instability high (pMMR or not MSI-H) mCRC. METHODS: In this international, multicenter, randomized, controlled, open-label, phase III study, eligible patients age 18 years and older with unresectable, pMMR or not MSI-H mCRC, that had progressed on or after, or could not tolerate, standard treatment, were randomly assigned 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 400 mg intravenously once every 6 weeks or investigator's choice of regorafenib or trifluridine/tipiracil (SOC). Randomization was stratified by presence or absence of liver metastases. The primary end point was overall survival (OS). LEAP-017 is registered at ClinicalTrials.gov (NCT04776148), and has completed recruitment. RESULTS: Between April 8, 2021, and December 21, 2021, 480 patients were randomly assigned to lenvatinib plus pembrolizumab (n = 241) or SOC (n = 239). At final analysis (median follow-up of 18.6 months [IQR, 3.9]), median OS with lenvatinib plus pembrolizumab versus SOC was 9.8 versus 9.3 months (hazard ratio [HR], 0.83 [95% CI, 0.68 to 1.02]; P = .0379; prespecified threshold P = .0214). Grade ≥3 treatment-related adverse events occurred in 58.4% (lenvatinib plus pembrolizumab) versus 42.1% (SOC) of patients. Two participants died due to treatment-related adverse events, both in the lenvatinib plus pembrolizumab arm. CONCLUSION: In patients with pMMR or not MSI-H mCRC that had progressed on previous therapy, there was no statistically significant improvement in OS after lenvatinib plus pembrolizumab treatment versus SOC. No new safety signals were observed.

Availability of services in Ontario hospices and hospitals providing inpatient palliative care.

PURPOSE: Most Canadians die in inpatient settings. Our aim was to determine the availability of medical services, programs, and care for common palliative procedures, in hospices, palliative care units (PCUs), and hospital medical wards (MWs) providing inpatient palliative care in Ontario, Canada. METHODS: We identified facilities providing inpatient palliative care using the Ontario Hospital Association (OHA) and Hospice Association of Ontario (HAO) websites. An electronic survey was sent to the person responsible for palliative care at each facility. We compared services available among the three types of units, using Fisher's exact and Kruskal-Wallis tests. RESULTS: Of 128 surveys sent, 102 (80%) were completed and returned, from 58 MWs, 31 PCUs, and 13 hospices. MWs were the most common location of palliative care overall, particularly in rural areas. PCUs were most likely to provide care for common procedures (e.g., tracheostomy, nephrostomy; p<0.01); methadone for pain management (p<0.0001); and palliative radiation (p<0.01). MWs were most likely to offer intravenous chemotherapy and antibiotics (p<0.01). Transfusions were available in most PCUs and MWs, but only in one hospice (p<0.0001). Hospices were most likely to provide complementary therapies. Lack of financial support and human resources were the most frequent perceived barriers to providing quality palliative care. CONCLUSIONS: There is considerable variability of available services depending on the setting where inpatient palliative care is provided. Further financial support and resources are required to ensure consistent high quality of care in both urban and rural areas.

Patient and physician perceptions on continuing aromatase inhibitors beyond the 5-year mark.

Aromatase inhibitors (AIs) have been shown to improve disease-free survival and in certain cases, overall survival in the treatment of postmenopausal women with hormone receptor positive early breast cancer. Trials are ongoing to determine if AI therapy should be continued for patients who have already completed 5 years of AI treatment. The objective of this study was to assess the minimum disease-free and overall survival benefit acceptable to physicians and to women undergoing AI therapy to continue treatment beyond 5 years. A self-administered survey was completed by women with stage I-III breast cancer, who were undergoing adjuvant AI therapy for at least 1 year. The survey assessed relevant cancer-related, treatment, social and comorbid factors, and FACT-ES (V4). Minimum acceptable treatment benefit was denoted as a percentage decrease in cancer recurrence risk, and percentage increase in survival at 5 years. Medical oncologists (MOs) treating breast cancer across Canada were also surveyed. A total of 153 patients were surveyed; median age was 60, 51% had node-negative disease, 89% had prior radiation therapy, 61% had prior chemotherapy, and 59% had prior tamoxifen therapy. Mean duration of AI therapy was 31 months. Approximately 30% of women required a 5-year survival benefit of less than 1%, and 27.5% needed a decrease in risk of recurrence of less than 1% to continue an AI beyond the initial 5 years. In contrast, 45% of the 40 surveyed MOs required a 5-year survival benefit of at least 1-2%, and 37.5% preferred a decrease in recurrence risk of 2-5% to prescribe an AI for an additional 5 years. There was a significant correlation between severity of endocrine symptoms experienced on AIs and an increased minimum survival benefit required for women to continue therapy (r = 0.18, p = 0.036). Patients were willing to continue on AIs for smaller treatment benefits than physicians would prefer to prescribe them beyond 5 years. Patient preference to continue on AIs correlated somewhat to the severity of AI-related side effects.