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Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are highly effective for treatment of EGFR- or ALK -mutated lung cancer. Nevertheless, they are associated with several unique toxicities. Although the available US Food and Drug Administration (FDA)-approved drug label can provide guidance for safety monitoring, its integration into clinical practice has not been previously described. We studied the conduct of safety monitoring activity (SMA) at a large academic institution. On the basis of FDA-approved drug labels, two drug-specific SMAs were identified for osimertinib, crizotinib, alectinib, or lorlatinib. Electronic medical records of patients initiated on these drugs from 2017 to 2021 were retrospectively reviewed. Each course of treatment was evaluated for the occurrence of SMAs and the corresponding adverse events. Analyses included 130 treatment courses from 111 unique patients. For each SMA evaluated, the prevalence of SMA conduct ranged from 10.0% to 84.6%. The most frequently conducted SMA was ECG for lorlatinib therapy and the least was creatine phosphokinase analysis for alectinib. We observed none of the assessed SMAs being conducted in 41 treatment courses (31.5%). EGFR inhibitor predicted a higher likelihood of both SMAs being conducted than ALK inhibitors ( P = .02). Serious, grade 3 or 4 adverse events were observed in 21 treatment courses (16.2%), including one grade 4 transaminitis related to alectinib. On the basis of our experience, the conduct of SMA was more challenging to implement for ALK inhibitor than for EGFR inhibitor. Clinicians should be vigilant and review the FDA-approved drug label before prescribing.

Next-generation sequencing (NGS) is rapidly expanding into routine oncology practice. Genetic variations in both the cancer and inherited genomes are informative for hereditary cancer risk, prognosis, and treatment strategies. Herein, we focus on the clinical perspective of integrating NGS results into patient care to assist with therapeutic decision making. Five key considerations are addressed for operationalization of NGS testing and application of results to patient care as follows: (1) NGS test ordering and workflow design; (2) result reporting, curation, and storage; (3) clinical consultation services that provide test interpretations and identify opportunities for molecularly guided therapy; (4) presentation of genetic information within the electronic health record; and (5) education of providers and patients. Several of these key considerations center on informatics tools that support NGS test ordering and referencing back to the results for therapeutic purposes. Clinical decision support tools embedded within the electronic health record can assist with NGS test utilization and identifying opportunities for targeted therapy including clinical trial eligibility. Challenges for project and change management in operationalizing NGS-supported, evidence-based patient care in the context of current information technology systems with appropriate clinical data standards are discussed, and solutions for overcoming barriers are provided., Competing Interests: The following represents disclosure information provided by the authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). J. Kevin Hicks Consulting or Advisory Role: Quest Diagnostics, 23andMe Research Funding: OneOmeKaren K. Fields Stock and Other Ownership Interests: Pfizer, AbbVie Honoraria: NCCN, NACCME, Pacific Group on Business, HMP, MJH Healthcare Holdings LLC Consulting or Advisory Role: United Health Group Speakers' Bureau: Genentech/Roche Travel, Accommodations, Expenses: Genentech/Roche, CBI, Discern Health, Tapestry, NACCME, Cigna Health Care, FLASCOJhanelle E. Gray Consulting or Advisory Role: Bristol Myers Squibb, EMD Serono, Inivata, Merck Sharp & Dohme, Axiom Healthcare Strategies, Novartis, AstraZeneca, Blueprint Medicines, Lilly, Sanofi, Janssen Scientific Affairs Research Funding: Array BioPharma, Merck, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Genentech/Roche, G1 Therapeutics, Novartis, Pfizer, Ludwig Institute for Cancer Research Travel, Accommodations, Expenses: Bristol Myers Squibb, Merck Sharp & Dohme, Inivata, Merck, EMD Serono, NovartisBryan McIver Honoraria: Eisai, Loxo/Lilly, Blueprint Medicines, Exelixis Consulting or Advisory Role: Eisai, Loxo/Lilly, Exelixis Speakers' Bureau: Loxo/LillyMandy F. O'Leary Stock and Other Ownership Interests: Bristol Myers SquibbRanda M. Perkins Stock and Other Ownership Interests: Progyny Other Relationship: Centene Open Payments Link: https://openpaymentsdata.cms.gov/physician/263299Jamie K. Teer Patents, Royalties, Other Intellectual Property: Patent application: Large Data Set Negative Information Storage ModelJoseph Markowitz Stock and Other Ownership Interests: Intel, Aflac, CVS, Amdocs, Consolidated Edison Honoraria: Springer Consulting or Advisory Role: Idera, Newlink Genetics, Array Biopharma Research Funding: Reata Pharmaceuticals, Macrogenics, Morphogenesis, Genoptix, Idera, Jackson Laboratory for Genomic Medicine, Merck Other Relationship: SpringerDana E. Rollison Leadership: NanoString Technologies Stock and Other Ownership Interests: NanoString Technologies Patents, Royalties, Other Intellectual Property: I am a co-inventor on a provisional patent application filed in July of 2020. The patent pertains to the use of spectrophotometer-measured UV radiation exposure in combination with regulatory T-cells measured in circulation to predict risk of subsequent skin cancer Travel, Accommodations, Expenses: Caserta Analytics Inc (not a healthcare company specifically, but they do business with healthcare companies), NanoString Technologies No other potential conflicts of interest were reported., (© 2021 by American Society of Clinical Oncology.)

It has recently been described that alternative oncogenic drivers may be found in KRAS wild-type ( KRAS WT ) pancreatic cancers. This study aimed to determine the incidence of targetable gene fusions present in KRAS WT pancreatic adenocarcinoma and response to targeted therapy., Methods: One hundred consecutive patients with pancreatic adenocarcinoma who underwent targeted next-generation sequencing using DNA sequencing with RNA sequencing (n = 47) or without RNA sequencing (n = 53) at a single institution were included in the study. The frequency and landscape of targetable fusions in KRAS WT pancreatic adenocarcinoma was characterized and compared with the frequency of fusions in KRAS -mutated ( KRAS MUT ) pancreatic adenocarcinoma. Results were validated in two independent cohorts using data from AACR GENIE (n = 1,252) and TCGA (n = 150). The clinical history of fusion-positive patients who received targeted treatment is described., Results: Pancreatic cancers from 13 of 100 patients (13%) were found to be KRAS WT . Targetable fusions were identified in 4/13 (31%) KRAS WT tumors compared with 0/87 (0%) KRAS MUT pancreatic adenocarcinomas ( P = .0002). One patient with a novel MET fusion had a complete response to targeted therapy with crizotinib that is ongoing at 12+ months of treatment. In the validation cohorts, gene fusions were identified in 18/97 (19%) and 2/10 (20%) KRAS WT tumors reported in the AACR GENIE and TCGA cohorts, respectively., Conclusion: Oncogene fusions are present in KRAS WT pancreatic adenocarcinomas at an increased frequency when compared with KRAS MUT pancreatic adenocarcinomas. As these fusions may be susceptible to targeted therapy, molecular analyses for the detection of fusions in KRAS WT pancreatic adenocarcinomas may warrant increased consideration., (© 2021 by American Society of Clinical Oncology.)