Regorafenib in Patients With Solid Tumors With BRAF Alterations: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

PURPOSE: Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer with genomic alterations known to be drug targets. Results of a cohort of patients with solid tumors with BRAF alterations treated with regorafenib are reported. METHODS: Eligible patients had measurable disease (RECIST v.1.1), Eastern Cooperative Oncology Group performance status 0-1, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as investigator assessment of patients with complete or partial response (PR) or stable disease of at least 16-weeks duration (SD16+). Low accruing histology-specific cohorts with BRAF alterations treated with regorafenib were collapsed into a single histology-pooled cohort for this analysis. The results were evaluated on the basis of a one-sided exact binomial test with a null DC rate of 15% versus 35% (power, 0.84; α, .10). Secondary end points were objective response (OR), progression-free survival, overall survival, duration of response, duration of stable disease, and safety. RESULTS: Twenty-eight patients with 12 tumor types with BRAF alterations were enrolled from June 2016 to June 2021. All patients were evaluable for efficacy. Two patients with PR and four with SD16+ were observed for DC and OR rates of 21% (90% CI, 12 to 100) and 7% (95% CI, 1 to 24), respectively. The null hypothesis of 15% DC rate was not rejected (P = .24). Eight patients had at least one grade 3 adverse event or serious adverse event at least possibly related to regorafenib. CONCLUSION: Regorafenib did not meet prespecified criteria to declare a signal of activity in patients with solid tumors with BRAF alterations.

Doxorubicin-induced cardiac toxicity and cardiac rest gated blood pool imaging.

Anthracyclines are one of the most commonly used and potent chemotherapeutic agents. Doxorubicin (Adriamycin) is one common anthracycline used to treat many solid tumors including breast, sarcomas, gynecologic and hematological malignancies, such as leukemias and lymphomas. However, its use is often limited due to dose-dependent cardiotoxicity. As a result, patients receiving doxorubicin should have close monitoring of their left ventricular function. The gated cardiac blood pool (GBP) study is one of the most accurate and reproducible methods of assessing left ventricular function. This report presents an overview of (1) the incidence, clinical course, mechanisms, pathology, prevention, and monitoring of doxorubicin-induced cardiotoxicity (DIC), (2) the use of GBP studies in monitoring for DIC, and (3) 2 algorithms for the use of GBP studies in monitoring for DIC. This report concludes with a proposed algorithm for the use of GBP studies in DIC. With an understanding of DIC, GBP studies, and various algorithms, the interpreting physician may help the oncologist identify DIC earlier, more accurately, and before it becomes clinically apparent.