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Exceptional Response to Crizotinib With Subsequent Response to Cabozantinib in Metastatic, ROS1-GOPC Fusion-Mutated Breast Cancer Discussion In this report we review a patient's course of treatment for ER-positive HER2-negative breast cancer harboring an activating I GOPC-ROS1 i fusion mutation that was exceptionally responsive to crizotinib therapy and had a subsequent modest response to cabozantinib after crizotinib resistance had occurred. I ROS1 i is a proto-oncogene that encodes a type I integral membrane protein with receptor tyrosine kinase (RTK) activity.[1] I ROS1 i arrangements are a well-recognized driver mutation present in up to 1%-2% of patients with non-small-cell lung cancer (NSCLC), with I CD74-ROS1 i fusion being the most common.[2] Actionable I ROS1 i mutations are exceptionally rare in breast cancer. [Extracted from the article]

PURPOSE: Tissue-based comprehensive genomic profiling (CGP) is increasingly used for treatment selection in patients with advanced cancer; however, tissue availability may limit widespread implementation. Here, we established real-world CGP tissue availability and assessed CGP performance on consecutively received samples. MATERIALS AND METHODS: We conducted a post hoc, nonprespecified analysis of 32,048 consecutive tumor tissue samples received for StrataNGS, a multiplex polymerase chain reaction (PCR)–based comprehensive genomic profiling (PCR-CGP) test, as part of an ongoing observational trial (NCT03061305). Sample characteristics and PCR-CGP performance were assessed across all tested samples, including exception samples not meeting minimum input quality control (QC) requirements (< 20% tumor content [TC], < 2 mm2 tumor surface area [TSA], DNA or RNA yield < 1 ng/µL, or specimen age > 5 years). Tests reporting ≥ 1 prioritized alteration or meeting TC and sequencing QC were considered successful. For prostate carcinoma and lung adenocarcinoma, tests reporting ≥ 1 actionable or informative alteration or meeting TC and sequencing QC were considered actionable. RESULTS: Among 31,165 (97.2%) samples where PCR-CGP was attempted, 10.7% had < 20% TC and 59.2% were small (< 25 mm2 tumor surface area). Of 31,101 samples evaluable for input requirements, 8,089 (26.0%) were exceptions not meeting requirements. However, 94.2% of the 31,101 tested samples were successfully reported, including 80.5% of exception samples. Positive predictive value of PCR-CGP for ERBB2 amplification in exceptions and/or sequencing QC-failure breast cancer samples was 96.7%. Importantly, 84.0% of tested prostate carcinomas and 87.9% of lung adenocarcinomas yielded results informing treatment selection. CONCLUSION: Most real-world tissue samples from patients with advanced cancer desiring CGP are limited, requiring optimized CGP approaches to produce meaningful results. An optimized PCR-CGP test, coupled with an inclusive exception testing policy, delivered reportable results for > 94% of samples, potentially expanding the proportion of CGP-testable patients and impact of biomarker-guided therapies. [ABSTRACT FROM AUTHOR]

The I MET i proto-oncogene encodes a receptor tyrosine kinase that is activated by binding of hepatocyte growth factor (HGF).[1] MET is oncogenically activated by either amplification or mutation in 7% of patients with non-small-cell lung cancer[2] and also less frequently in other solid tumor types. Of 925 patients with breast cancer evaluated for copy number alterations in the Cancer Genome Atlas study, only eight patients (0.86%) had I MET i amplification.[4] 7 Jenkins RW Oxnard GR Elkin Set al: Response to crizotinib in a patient with lung adenocarcinoma harboring a MET splice site mutation. 12 Schwab R Petak I Kollar Met al: Major partial response to crizotinib, a dual MET/ALK inhibitor, in a squamous cell lung (SCC) carcinoma patient with de novo c-MET amplification in the absence of ALK rearrangement. [Extracted from the article]

Purpose: Precision oncology develops and implements evidence-based personalized therapies that are based on specific genetic targets within each tumor. However, a major challenge that remains is the provision of a standardized, up-to-date, and evidenced-based precision medicine initiative across a geographic region. Materials and Methods: We developed a statewide molecular tumor board that integrates academic and community oncology practices. The Precision Medicine Molecular Tumor Board (PMMTB) has three components: a biweekly Web-based teleconference tumor board meeting provided as a free clinical service, an observational research registry, and a monthly journal club to establish and revise evidence-based guidelines for off-label therapies. The PMMTB allows for flexible and rapid implementation of treatment, uniformity in practice, and the ability to track outcomes. Results: We describe the implementation of the PMMTB and its first year of activity. Seventy-seven patient cases were presented, 48 were enrolled in a registry, and 38 had recommendations and clinical follow-up. The 38 subjects had diverse solid tumors (lung, 45%; GI, 21%; breast, 13%; other, 21%). Of these subjects, targeted therapy was recommended for 32 (84%). Clinical trials were identified for 24 subjects (63%), and nontrial targeted medicines for 16 (42%). Nine subjects (28%) received recommended therapy with a response rate of 17% (one of six) and a clinical benefit rate (partial response + stable disease) of 38% (three of eight). Although clinical trials often were identified, patients rarely enrolled. Conclusion: The PMMTB provides a model for a regional molecular tumor board with clinical utility. This work highlights the need for outcome registries and improved access to clinical trials to pragmatically implement precision oncology. [ABSTRACT FROM AUTHOR]