Microsatellite instability (MSI) is caused by mutations in the DNA mismatch repair genes and has been shown to predict response to checkpoint inhibitors (CPIs). Both FDA & EMA have approved CPIs in MSI-High (MSI-H) colorectal cancer (CRC). The aim of this study was to understand MSI testing practices for CRC patients, among physicians in Europe and Asia. This study was conducted using Oncology DynamicsTM, an online market research physician survey collecting drug-treated, anonymized patient data. 8,104 CRC patients in France, Germany, Italy, Spain, & UK and 4,459 CRC patients in China, Japan, & S. Korea were analyzed, in 2021, excluding clinical trials. MSI test method was available only for Q3+Q4 2021. Overall MSI testing rate was higher in Europe (44%) than Asia (35%). In Europe, the highest uptake of MSI test was observed in France and Spain at 57% and 54% testing rates, respectively. In Asia, South Korea reported the highest testing rate (68%). Among tested patients, Europe reported higher proportion (11%) of MSI-H patients compared to Asia (6%). At country level, the MSI-H patients ranged from 7-14% in Europe and 3-7% in Asia. 38% of MSI-H patients in Europe and 24% of MSI-H patients in Asia were treated with CPIs, in first-line setting. MSI test method was investigated for 1,560 patients in Europe and 782 patients in Asia, in Q3+Q4 2021. Among these patients, we have information on test method for 1,167 (75%) patients in Europe and 684 (87%) patients in Asia. In both regions, Polymerase Chain Reaction (PCR) was the predominant method of MSI detection, with 72% and 67% patient share in Europe and Asia, respectively. Next-Generation Sequencing (NGS) was used in 23-25% patients, in both regions. Highest use of NGS was observed in China (37%), followed by France (34%). This study demonstrated that testing rates are still suboptimal, reflecting barriers to testing MSI in CRC patients, in Europe and Asia. This study identifies the need for more communication and education about the benefits of testing to improve testing rates and treatment decisions. Further evaluation of the NGS adoption in clinical practice is warranted.

Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/ mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade >3 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design.

Background P + H + docetaxel (DOC) is the standard first-line therapy for HER2-positive LR/mBC, based on results from the phase 3 CLEOPATRA trial. The single-arm PERUSE study (NCT01572038) assessed the safety and efficacy of P + H with investigator-selected taxane in this setting. We present final safety and efficacy results.

Background: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. Patients and methods: In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8 mg/kg loading dose, then 6 mg/kg every 3 weeks (q3w)] and pertuzumab (840 mg loading dose, then 420 mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). Results: Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54 years; 29% had received prior trastuzumab. Median treatment duration was 16 months for pertuzumab and trastuzumab and 4 months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1 months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). Conclusions: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile.