RESUMO
PURPOSE: The TAPUR Study is a pragmatic phase II basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from two cohorts of patients with colorectal cancer (CRC) with either ERBB2 amplifications or ERBB2 or ERBB3 (ERBB2/3) mutations treated with pertuzumab plus trastuzumab (P + T) are reported. METHODS: Eligible patients with measurable CRC were selected for treatment with P + T according to protocol-specified genomic matching rules. Patients had no remaining standard treatment options, Eastern Cooperative Oncology Group performance status 0-2, and adequate organ function. Simon's two-stage design was used with a primary study end point of disease control (DC; objective response [OR] or stable disease of at least 16 weeks duration [SD16+]). Secondary end points include safety, response duration, progression-free survival (PFS), and overall survival (OS). RESULTS: Thirty-eight patients with CRC with ERBB2 amplification (N = 28) or ERBB2/3 mutations (N = 10) were treated with P + T. For the ERBB2 amplification cohort, DC and OR were observed in 54% and 25% of patients, respectively; the median PFS and median OS (95% CIs) were 17.2 (11.1 to 27.4) weeks and 60.0 (32.1 to 102.3) weeks, respectively. For the ERBB2/3 mutation cohort, DC and OR were observed in 10% and 0% of patients, respectively; the median PFS and median OS were 9.6 (5.1 to 16.0) weeks and 28.8 (7.6 to 146.3) weeks, respectively. Four of 38 patients experienced grade 3 adverse events or serious adverse events including anemia, infusion reaction, diarrhea, left ventricular systolic dysfunction, and decreased lymphocyte count. CONCLUSION: Although P + T treatment does not appear to have antitumor activity in CRC with ERBB2/3 mutations, this combination has antitumor activity in patients with CRC with ERBB2 amplification and warrants further study.