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Purpose: Cancer clinical trials often accrue slowly or miss enrollment targets. Strict eligibility criteria are a major reason. Restrictive criteria also limit opportunities for patient participation while compromising external validity of trial results. We examined the impact of broadening select eligibility criteria on characteristics and number of patients eligible for trials, using recommendations of the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research., Experimental Design: A retrospective, observational analysis used electronic health record data from ASCO's CancerLinQ Discovery database. Study cohort included patients with advanced non-small cell lung cancer treated from 2011 to 2018. Patients were grouped by traditional criteria [no brain metastases, no other malignancies, and creatinine clearance (CrCl) ≥ 60 mL/minute] and broadened criteria (including brain metastases, other malignancies, and CrCl ≥ 30 mL/minute)., Results: The analysis cohort included 10,500 patients. Median age was 68 years, and 73% of patients were White. Most patients had stage IV disease (65%). A total of 5,005 patients (48%) would be excluded from trial participation using the traditional criteria. The broadened criteria, however, would allow 98% of patients (10,346) to be potential participants. Examination of patients included by traditional criteria (5,495) versus those added (4,851) by broadened criteria showed that the number of women, patients aged 75+ years, and those with stage IV cancer was significantly greater using broadened criteria., Conclusions: This analysis of real-world data demonstrated that broadening three common eligibility criteria has the potential to double the eligible patient population and include trial participants who are more representative of those encountered in practice. See related commentary by Giantonio, p. 2369 ., (©2021 American Association for Cancer Research.)

On October 18, 2016, the FDA approved atezolizumab (TECENTRIQ; Genentech, Inc.) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose disease progressed during or following platinum-containing chemotherapy. Approval was based on demonstration of clinically meaningful improvements in overall survival (OS) and an acceptable safety profile in two randomized clinical trials (OAK and POPLAR). Median OS in OAK, a phase III trial, was 13.8 months [95% confidence interval (CI), 11.8-15.7] in the atezolizumab arm compared with 9.6 months (95% CI, 8.6-11.2) in the docetaxel arm [hazard ratio (HR) = 0.74; 95% CI, 0.63-0.87; P = 0.0004]. Median OS in POPLAR, a phase II trial, was 12.6 months (95% CI, 9.7-16.0) and 9.7 months (95% CI, 8.6-12.0; HR = 0.69; 95% CI, 0.52-0.92) for the atezolizumab and docetaxel arms, respectively. In patients treated with atezolizumab, the most common (≥20%) adverse reactions were fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation; the most common (≥2%) grade 3 to 4 adverse events were dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, aspartate aminotransferase increase, alanine aminotransferase increase, dysphagia, and arthralgia. Clinically significant immune-related adverse events for patients receiving atezolizumab included 1.4% incidence each of grade 3 to 4 pneumonitis, hepatitis, colitis, and thyroid disease. Clin Cancer Res; 23(16); 4534-9. ©2017 AACR ., (©2017 American Association for Cancer Research.)

On November 13, 2015, the FDA granted accelerated approval to osimertinib (TAGRISSO; AstraZeneca), a breakthrough therapy-designated drug for the treatment of patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer, as detected by an FDA-approved test, with progression on or after EGFR tyrosine kinase inhibitor therapy. Approval was based on durable tumor response rates in two single-arm, multicenter trials: the dose extension cohort of a first-in-human trial (FIH; AURA extension; n = 201) and a fixed-dose, activity-estimating trial (AURA2; n = 210). Osimertinib was administered at 80 mg orally once daily. The objective response rates (ORR) per blinded independent committee review were 57% [95% confidence interval (CI), 50-64) in AURA extension and 61% (95% CI, 54-68) in AURA2. Median duration of response (DOR) could not be estimated. Supportive efficacy data from 63 patients in the dose-finding part of the FIH trial demonstrated an ORR of 51% (95% CI, 38-64), with a median DOR of 12.4 months. Common adverse events (AE) evaluated in 411 patients included diarrhea (42%), rash (41%), dry skin (31%), and nail toxicity (25%). Grade 3 to 4 AEs occurred in 28% of patients, and 5.6% discontinued treatment due to AEs. Clin Cancer Res; 23(9); 2131-5. ©2016 AACR ., (©2016 American Association for Cancer Research.)

Sponsors of human drug and biologic products subject to an investigational new drug (IND) application are required to distribute expedited safety reports of serious and unexpected suspected adverse reactions to participating investigators and the FDA to assure the protection of human subjects participating in clinical trials. On September 29, 2010, the FDA issued a final rule amending its regulations governing expedited IND safety reporting requirements that revised the definitions used for reporting and clarified when to submit relevant and useful information to reduce the number of uninformative reports distributed by sponsors. From January 1, 2006, to December 31, 2014, the FDA's Office of Hematology and Oncology Products received an average of 17,686 expedited safety reports per year. An analysis of FDA submissions by commercial sponsors covering this time period suggested a slight increase in the number of expedited safety reports per IND per year after publication of the final rule. An audit of 160 randomly selected expedited safety reports submitted to the FDA's Office of Hematology and Oncology Products in 2015 revealed that only 22 (14%) were informative. The submission of uninformative expedited safety reports by commercial sponsors of INDs continues to be a significant problem that can compromise detection of valid safety signals. Clin Cancer Res; 22(9); 2111-3. ©2016 AACR., (©2016 American Association for Cancer Research.)

On April 29, 2014, the FDA granted accelerated approval to ceritinib (ZYKADIA; Novartis Pharmaceuticals Corporation), a breakthrough therapy-designated drug, for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. The approval was based on a single-arm multicenter trial enrolling 163 patients with metastatic ALK-positive NSCLC who had disease progression on (91%) or intolerance to crizotinib. Patients received ceritinib at a starting dose of 750 mg orally once daily. The objective response rate (ORR) by a blinded independent review committee was 44% (95% CI, 36-52), and the median duration of response (DOR) was 7.1 months. The ORR by investigator assessment was similar. Safety was evaluated in 255 patients. The most common adverse reactions and laboratory abnormalities included diarrhea (86%), nausea (80%), increased alanine transaminase (80%), increased aspartate transaminase (75%), vomiting (60%), increased glucose (49%), and increased lipase (28%). Although 74% of patients required at least one dose reduction or interruption due to adverse reactions, the discontinuation rate due to adverse reactions was low (10%). With this safety profile, the benefit-risk analysis was considered favorable because of the clinically meaningful ORR and DOR., (©2015 American Association for Cancer Research.)

Purpose: There are limited data regarding the role of (18)F-fluorodeoxyglucose positron emission tomography ([(18)F]-FDG PET) imaging in management of patients with thymic epithelial tumors (TET). The primary objective of this study was to assess the usefulness of early [(18)F]-FDG PET to monitor treatment efficacy and its correlation with Response Evaluation Criteria in Solid Tumors (RECIST) in patients with TETs., Experimental Design: [(18)F]-FDG PET/computed tomographic (CT) scans were conducted at baseline and after 6 weeks of treatment in patients enrolled in two phase II and one phase I/II clinical trials. On the basis of data from other solid tumors, metabolic response was defined as a reduction of [(18)F]-FDG uptake by more than 30% as assessed by average standardized uptake values (SUV) of up to five most metabolically active lesions., Results: Fifty-six patients with unresectable Masaoka stage III or IV TETs were included. There was a close correlation between early metabolic response and subsequent best response using RECIST (P < 0.0001-0.0003): sensitivity and specificity for prediction of best response were 95% and 100%, respectively. Metabolic responders had significantly longer progression-free survival (median, 11.5 vs. 4.6 months; P = 0.044) and a trend toward longer overall survival (median, 31.8 vs. 18.4 months; P = 0.14) than nonresponders. [(18)F]-FDG uptake was significantly higher in thymic carcinoma than in thymoma (P = 0.0004-0.0010)., Conclusion: In patients with advanced TETs, early metabolic response closely correlates with outcome of therapy. [(18)F]-FDG PET may be used to monitor treatment efficacy and assess histologic differences in patients with advanced TETs.