Professor of Medicine, Director of Thoracic Medical Oncology Program, Director of Early Clinical Trials, Experimental Therapeutics Research Program, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA
Dr. Christian Rolfo
Professor of Medicine, Director of Thoracic Medical Oncology Program, Director of Early Clinical Trials, Experimental Therapeutics Research Program, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA
Activating mutations in the epidermal growth factor receptor gene (EGFR) confer hypersensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in patients with advanced non–small-cell lung cancer. We evaluated the feasibility of large-scale screening for EGFR mutations in such patients and analyzed the association between the mutations and the outcome of erlotinib treatment.
PURPOSE: The COVID-19 pandemic affected health care systems globally and resulted in the interruption of usual care in many health care facilities, exposing vulnerable patients with cancer to significant risks. Our study aimed to evaluate the impact of this pandemic on cancer care worldwide. METHODS: We conducted a cross-sectional study using a validated web-based questionnaire of 51 items. The questionnaire obtained information on the capacity and services offered at these centers, magnitude of disruption of care, reasons for disruption, challenges faced, interventions implemented, and the estimation of patient harm during the pandemic. RESULTS: A total of 356 centers from 54 countries across six continents participated between April 21 and May 8, 2020. These centers serve 716,979 new patients with cancer a year. Most of them (88.2%) reported facing challenges in delivering care during the pandemic. Although 55.34% reduced services as part of a preemptive strategy, other common reasons included an overwhelmed system (19.94%), lack of personal protective equipment (19.10%), staff shortage (17.98%), and restricted access to medications (9.83%). Missing at least one cycle of therapy by > 10% of patients was reported in 46.31% of the centers. Participants reported patient exposure to harm from interruption of cancer-specific care (36.52%) and noncancer-related care (39.04%), with some centers estimating that up to 80% of their patients were exposed to harm. CONCLUSION: The detrimental impact of the COVID-19 pandemic on cancer care is widespread, with varying magnitude among centers worldwide. Additional research to assess this impact at the patient level is required.
Purpose: Entrectinib potently inhibits tropomyosin receptor kinases (TRKAs)/B/C and ROS1, and previously induced deep [objective response rate (ORR) 57.4%] and durable [median duration of response (DoR) 10.4 months] responses in adults with NTRK fusion-positive solid tumors from three phase I/II trials. This article expands prior reports with additional patients and longer follow-up. Patients and Methods: Patients with locally advanced/metastatic NTRK fusion-positive solid tumors and ≥12 months' follow-up were included. Primary endpoints were ORR and DoR by blinded independent central review (BICR); secondary endpoints included progression-free survival (PFS), intracranial efficacy, and safety. The safety-evaluable populations included all patients who had received ≥1 entrectinib dose. Results: At clinical cut-off (August 31, 2020), the efficacy-evaluable population comprised 121 adults with 14 tumor types and ≥30 histologies. Median follow-up was 25.8 months; 61.2% of patients had a complete (n = 19) or partial response (n = 55). Median DoR was 20.0 months [95% confidence interval (CI), 13.0–38.2]; median PFS was 13.8 months (95% CI, 10.1–19.9). In 11 patients with BICR-assessed measurable central nervous system (CNS) disease, intracranial ORR was 63.6% (95% CI, 30.8–89.1) and median intracranial DoR was 22.1 (95% CI, 7.4–not estimable) months. The safety profile of entrectinib in adults and pediatric patients was aligned with previous reports. Most treatment-related adverse events (TRAEs) were grade 1/2 and manageable/reversible with dose modifications. TRAE-related discontinuations occurred in 8.3% of patients. Conclusions: With additional clinical experience, entrectinib continues to demonstrate durable systemic and intracranial responses and can address the unmet need of a CNS-active treatment in patients with NTRK fusion-positive solid tumors.