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N Engl J Med ; 387(2): 120-131, 2022 07 14.
Article in English | MEDLINE | ID: covidwho-1967704


BACKGROUND: Adagrasib, a KRASG12C inhibitor, irreversibly and selectively binds KRASG12C, locking it in its inactive state. Adagrasib showed clinical activity and had an acceptable adverse-event profile in the phase 1-1b part of the KRYSTAL-1 phase 1-2 study. METHODS: In a registrational phase 2 cohort, we evaluated adagrasib (600 mg orally twice daily) in patients with KRASG12C -mutated non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy and anti-programmed death 1 or programmed death ligand 1 therapy. The primary end point was objective response assessed by blinded independent central review. Secondary end points included the duration of response, progression-free survival, overall survival, and safety. RESULTS: As of October 15, 2021, a total of 116 patients with KRASG12C -mutated NSCLC had been treated (median follow-up, 12.9 months); 98.3% had previously received both chemotherapy and immunotherapy. Of 112 patients with measurable disease at baseline, 48 (42.9%) had a confirmed objective response. The median duration of response was 8.5 months (95% confidence interval [CI], 6.2 to 13.8), and the median progression-free survival was 6.5 months (95% CI, 4.7 to 8.4). As of January 15, 2022 (median follow-up, 15.6 months), the median overall survival was 12.6 months (95% CI, 9.2 to 19.2). Among 33 patients with previously treated, stable central nervous system metastases, the intracranial confirmed objective response rate was 33.3% (95% CI, 18.0 to 51.8). Treatment-related adverse events occurred in 97.4% of the patients - grade 1 or 2 in 52.6% and grade 3 or higher in 44.8% (including two grade 5 events) - and resulted in drug discontinuation in 6.9% of patients. CONCLUSIONS: In patients with previously treated KRASG12C -mutated NSCLC, adagrasib showed clinical efficacy without new safety signals. (Funded by Mirati Therapeutics; number, NCT03785249.).

Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Proto-Oncogene Proteins p21(ras) , Acetonitriles/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Piperazines/therapeutic use , Proto-Oncogene Proteins p21(ras)/antagonists & inhibitors , Proto-Oncogene Proteins p21(ras)/genetics , Pyrimidines/therapeutic use
Cancer Rep (Hoboken) ; 4(5): e1388, 2021 10.
Article in English | MEDLINE | ID: covidwho-1235659


BACKGROUND: The understanding of the impact of COVID-19 in patients with cancer is evolving, with need for rapid analysis. AIMS: This study aims to compare the clinical and demographic characteristics of patients with cancer (with and without COVID-19) and characterize the clinical outcomes of patients with COVID-19 and cancer. METHODS AND RESULTS: Real-world data (RWD) from two health systems were used to identify 146 702 adults diagnosed with cancer between 2015 and 2020; 1267 COVID-19 cases were identified between February 1 and July 30, 2020. Demographic, clinical, and socioeconomic characteristics were extracted. Incidence of all-cause mortality, hospitalizations, and invasive respiratory support was assessed between February 1 and August 14, 2020. Among patients with cancer, patients with COVID-19 were more likely to be Non-Hispanic black (NHB), have active cancer, have comorbidities, and/or live in zip codes with median household income <$30 000. Patients with COVID-19 living in lower-income areas and NHB patients were at greatest risk for hospitalization from pneumonia, fluid and electrolyte disorders, cough, respiratory failure, and acute renal failure and were more likely to receive hydroxychloroquine. All-cause mortality, hospital admission, and invasive respiratory support were more frequent among patients with cancer and COVID-19. Male sex, increasing age, living in zip codes with median household income <$30 000, history of pulmonary circulation disorders, and recent treatment with immune checkpoint inhibitors or chemotherapy were associated with greater odds of all-cause mortality in multivariable logistic regression models. CONCLUSION: RWD can be rapidly leveraged to understand urgent healthcare challenges. Patients with cancer are more vulnerable to COVID-19 effects, especially in the setting of active cancer and comorbidities, with additional risk observed in NHB patients and those living in zip codes with median household income <$30 000.

COVID-19/epidemiology , Neoplasms/epidemiology , Social Determinants of Health/statistics & numerical data , Socioeconomic Factors , Aged , COVID-19/diagnosis , COVID-19/therapy , COVID-19/virology , Comorbidity , Data Analysis , Female , Hospital Mortality , Humans , Male , Middle Aged , Neoplasms/complications , Neoplasms/immunology , Patient Admission/statistics & numerical data , Respiration, Artificial , Retrospective Studies , Risk Factors , SARS-CoV-2/immunology , Severity of Illness Index , United States/epidemiology
J Thorac Oncol ; 15(7): 1137-1146, 2020 07.
Article in English | MEDLINE | ID: covidwho-324987


The coronavirus disease 2019 (COVID-19) pandemic is currently accelerating. Patients with locally advanced NSCLC (LA-NSCLC) may require treatment in locations where resources are limited, and the prevalence of infection is high. Patients with LA-NSCLC frequently present with comorbidities that increase the risk of severe morbidity and mortality from COVID-19. These risks may be further increased by treatments for LA-NSCLC. Although guiding data is scarce, we present an expert thoracic oncology multidisciplinary (radiation oncology, medical oncology, surgical oncology) consensus of alternative strategies for the treatment of LA-NSCLC during a pandemic. The overarching goals of these approaches are the following: (1) reduce the number of visits to a health care facility, (2) reduce the risk of exposure to severe acute respiratory syndrome-coronavirus-2, (3) attenuate the immunocompromising effects of lung cancer therapies, and (4) provide effective oncologic therapy. Patients with resectable disease can be treated with definitive nonoperative management if surgical resources are limited or the risks of perioperative care are high. Nonoperative options include chemotherapy, chemoimmunotherapy, and radiation therapy with sequential schedules that may or may not affect long-term outcomes in an era in which immunotherapy is available. The order of treatments may be on the basis of patient factors and clinical resources. Whenever radiation therapy is delivered without concurrent chemotherapy, hypofractionated schedules are appropriate. For patients who are confirmed to have COVID-19, usually, cancer therapies may be withheld until symptoms have resolved with negative viral test results. The risk of severe treatment-related morbidity and mortality is increased for patients undergoing treatment for LA-NSCLC during the COVID-19 pandemic. Adapting alternative treatment strategies as quickly as possible may save lives and should be implemented through communication with the multidisciplinary cancer team.

Carcinoma, Non-Small-Cell Lung , Coronavirus Infections , Critical Pathways , Pandemics , Patient Care Management/methods , Pneumonia, Viral , Betacoronavirus/isolation & purification , COVID-19 , Carcinoma, Non-Small-Cell Lung/epidemiology , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Comorbidity , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Critical Pathways/organization & administration , Critical Pathways/trends , Humans , Infection Control/methods , Interdisciplinary Communication , Neoplasm Staging , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Risk Assessment , Risk Management/organization & administration , SARS-CoV-2