Neoadjuvant cemiplimab for resectable hepatocellular carcinoma: a single-arm, open-label, phase 2 trial.

BACKGROUND: Surgical resection of early stage hepatocellular carcinoma is standard clinical practice; however, most tumours recur despite surgery, and no perioperative intervention has shown a survival benefit. Neoadjuvant immunotherapy has induced pathological responses in multiple tumour types and might decrease the risk of postoperative recurrence in hepatocellular carcinoma. We aimed to evaluate the clinical activity of neoadjuvant cemiplimab (an anti-PD-1) in patients with resectable hepatocellular carcinoma. METHODS: For this single-arm, open-label, phase 2 trial, patients with resectable hepatocellular carcinoma (stage Ib, II, and IIIb) were enrolled and received two cycles of neoadjuvant cemiplimab 350 mg intravenously every 3 weeks followed by surgical resection. Eligible patients were aged 18 years or older, had confirmed resectable hepatocellular carcinoma, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate liver function. Patients were excluded if they had metastatic disease, if the surgery was not expected to be curative, if they had a known additional malignancy requiring active treatment, or if they required systemic steroid treatment or any other immunosuppressive therapy. After resection, patients received an additional eight cycles of cemiplimab 350 mg intravenously every 3 weeks in the adjuvant setting. The primary endpoint was significant tumour necrosis on pathological examination (defined as >70% necrosis of the resected tumour). Secondary endpoints included delay of surgery, the proportion of patients with an overall response, change in CD8+ T-cell density, and adverse events. Tumour necrosis and response were analysed in all patients who received at least one dose of cemiplimab and completed surgical resection; safety and other endpoints were analysed in the intention-to-treat population. Patients underwent pre-treatment biopsies and blood collection throughout treatment. This trial is registered with ClinicalTrials.gov (NCT03916627, Cohort B) and is ongoing. FINDINGS: Between Aug 5, 2019, and Nov 25, 2020, 21 patients were enrolled. All patients received neoadjuvant cemiplimab, and 20 patients underwent successful resection. Of the 20 patients with resected tumours, four (20%) had significant tumour necrosis. Three (15%) of 20 patients had a partial response, and all other patients maintained stable disease. 20 (95%) patients had a treatment-emergent adverse event of any grade during the neoadjuvant treatment period. The most common adverse events of any grade were increased aspartate aminotransferase (in four patients), increased blood creatine phosphokinase (in three), constipation (in three), and fatigue (in three). Seven patients had grade 3 adverse events, including increased blood creatine phosphokinase (in two patients) and hypoalbuminaemia (in one). No grade 4 or 5 events were observed. One patient developed pneumonitis, which led to a delay in surgery by 2 weeks. INTERPRETATION: This report is, to our knowledge, the largest clinical trial of a neoadjuvant anti-PD-1 monotherapy reported to date in hepatocellular carcinoma. The observed pathological responses to cemiplimab in this cohort support the design of larger trials to identify the optimal treatment duration and definitively establish the clinical benefit of preoperative PD-1 blockade in patients with hepatocellular carcinoma. FUNDING: Regeneron Pharmaceuticals.

Care disruptions among patients with lung cancer: A COVID-19 and cancer outcomes study.

INTRODUCTION: Patients with lung cancer (LC) are susceptible to severe outcomes from COVID-19. This study evaluated disruption to care of patients with LC during the COVID-19 pandemic. METHODS: The COVID-19 and Cancer Outcomes Study (CCOS) is a prospective cohort study comprised of patients with a current or past history of hematological or solid malignancies with outpatient visits between March 2 and March 6, 2020, at two academic cancer centers in the Northeastern United States (US). Data was collected for the three months prior to the index week (baseline period) and the following three months (pandemic period). RESULTS: 313 of 2365 patients had LC, 1578 had other solid tumors, and 474 had hematological malignancies. Patients with LC were not at increased risk of COVID-19 diagnosis compared to patients with other solid or hematological malignancies. When comparing data from the pandemic period to the baseline period, patients with LC were more likely to have a decrease in in-person visits compared to patients with other solid tumors (aOR 1.94; 95% CI, 1.46-2.58), but without an increase in telehealth visits (aOR 1.13; 95% CI 0.85-1.50). Patients with LC were more likely to experience pandemic-related treatment delays than patients with other solid tumors (aOR 1.80; 95% CI 1.13-2.80) and were more likely to experience imaging/diagnostic procedure delays than patients with other solid tumors (aOR 2.59; 95% CI, 1.46-4.47) and hematological malignancies (aOR 2.01; 95% CI, 1.02-3.93). Among patients on systemic therapy, patients with LC were also at increased risk for decreased in-person visits and increased treatment delays compared to those with other solid tumors. DISCUSSION: Patients with LC experienced increased cancer care disruption compared to patients with other malignancies during the early phase of the COVID-19 pandemic. Focused efforts to ensure continuity of care for this patient population are warranted.