Pertuzumab plus trastuzumab (P+T) in patients (Pts) with colorectal cancer (CRC) with ERBB2 amplification or overexpression: Results from the TAPUR Study.

Abstract

132 Background: TAPUR is a phase II basket trial evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of CRC pts with ERBB2 overexpression or amplification treated with P+T are reported. Methods: Eligible pts had advanced CRC, no standard treatment (tx) options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts had ERBB2 overexpression or amplification, or certain ERBB2 mutations. Recommended dosing after initial dosing was P, 420 mg IV over 30-60 mins every 3 weeks (wks) and T, 6 mg/kg over 30-60 mins every 3 wks. Simon two-stage design was used to test a null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16+ wks per RECIST (SD16+)), 18 more pts enrolled. If ≥7 of 28 pts have DC, the tx is worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Twenty-eight pts enrolled from November 2016 to September 2018 were evaluable for efficacy and safety. Demographics and outcomes are summarized in Table. All pts had ERBB2 amplification; 1 also had an ERBB2 mutation. 79% of pts had at least 3 prior txs. Four PR and 10 SD16+ were observed for DC and OR rates of 50% (90% CI, 36% to 60%) and 14% (95% CI, 4% to 33%), respectively. Two pts had at least one grade 3 AE or SAE at least possibly related to P+T including anemia, infusion reaction, and left ventricular dysfunction. Conclusions: The combination of P+T showed anti-tumor activity in heavily pre-treated CRC pts with ERBB2 amplification . Additional analyses by RAS mutation status are pending. Further study is warranted to confirm efficacy of P+T in this population. Clinical trial information: NCT02693535. [Table: see text]

Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

“…Another phase II basket study, TAPUR, also investigated the combination of trastuzumab and pertuzumab in HER2-amplified mCRC. 302 In this study, 28 patients with heavily pretreated, HER2-amplified advanced CRC were treated with the combination. Four partial responses and 10 cases of stable disease for at least 16 weeks were reported, leading to a disease control rate of 50% and an ORR of 14%.…”

Clinical Utility of Next-Generation Sequencing-Based Panel Testing under the Universal Health-Care System in Japan: A Retrospective Analysis at a Single University Hospital

“…For example, the Molecular Screening for Cancer Treatment Optimization (MOSCATO 01) study demonstrated that targeted therapy, which was matched to a genomic alteration, improved the survival of 33% (63/193) of the study participants [ 4 ]. In addition, in the Targeted Agent and Profiling Utilization Registry (TAPUR) study, genomically matched treatment showed good clinical efficacy in the following five cohorts: pertuzumab and trastuzumab in ERBB2 -amplified or overexpressed colorectal cancer [ 6 ], emurafenib and cobimetinib in BRAF V600E/D/K/-mutated colorectal cancer [ 7 ], pembrolizumab in metastatic breast cancer with a high mutational burden [ 8 ], pembrolizumab in metastatic colorectal cancer with a high mutational burden, and palbociclib in non-small cell lung cancer with CDKN2A alteration [ 9 , 10 ].…”

Pertuzumab and trastuzumab emtansine in patients with HER2-amplified metastatic colorectal cancer: the phase II HERACLES-B trial

“…The 9.7% ORR achieved by HERACLES-B regimen, lower than the 30% in HERACLES-A, should not dampen the interest for target-treating HER2+ mCRC; on the contrary, it underlines that several effective therapeutic options are at hand, including trastuzumab-based combinations with either small molecules tyrosine kinase inhibitors 7 or monoclonal antibody, such as pertuzumab aimed, at different epitopes. 17 24 Interestingly, recent data of the HER2+ mCRC arm of the Targeted Agent and Profiling Utilisation Registry study showed despite a higher ORR (25%) with the combination of trastuzumab and pertuzumab, 25 as data of the KRAS wild-type cohort of the MyPathway trial, a similar PFS of 4.3 months, once again indicating that a maintained disease control may be indicative of the antitumour potential of a HER2 therapeutic blockade. Other emerging therapeutic strategies include the development of more potent anti-HER2 agents, 26 such as bispecific antibodies which can bind two non-overlapping epitopes on HER2 or engage immune mediators together with HER2 binding, and novel antibody-drug conjugates such as trastuzumab deruxtecan.…”