The efficacy and safety of pertuzumab plus trastuzumab and docetaxel as a first-line therapy in Japanese patients with inoperable or recurrent HER2-positive breast cancer: the COMACHI study

Abstract

Purpose In the CLEOPATRA study of patients with human epidermal growth factor receptor 2 (HER2)-positive recurrent or metastatic breast cancer, the Japanese patient subgroup did not demonstrate the improved progression-free survival (PFS) of pertuzumab plus trastuzumab and docetaxel vs. placebo that was seen in the overall population. Therefore, COMACHI was conducted to confirm the efficacy and safety of this treatment regimen in this patient subgroup. Methods This was a phase IV study of pertuzumab plus trastuzumab and docetaxel in Japanese patients with histologically/cytologically confirmed inoperable or recurrent HER2-positive breast cancer. All patients received pertuzumab, trastuzumab, and docetaxel intravenously every 3 weeks until disease progression/unacceptable toxicity. The primary endpoint was investigator-assessed PFS. Secondary endpoints were overall survival (OS), investigator-assessed objective response rate, and duration of response (DoR). Safety was also assessed. Results At final analysis, median investigator-assessed PFS was 22.8 months (95% CI 16.9–37.5). From first dose, OS rate at 1 year was 97.7%; and at 2 and 3 years were 88.5% and 79.1%, respectively. Of the 118 patients with measurable disease at baseline, response rate was 83.9% (95% CI 77.3–90.5) and median investigator-assessed DoR was 26.3 months (95% CI 17.1–not evaluable). Treatment was well tolerated, with no new safety signals detected. Conclusions Our results suggest similar efficacy and safety for pertuzumab plus trastuzumab and docetaxel in Japanese patients compared with the overall population of CLEOPATRA, providing further support for this combination therapy as standard of care for Japanese patients with inoperable or recurrent HER2-positive breast cancer.

Comparative Effectiveness and Safety of Pertuzumab and Trastuzumab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy for Treatment of Metastatic Breast Cancer

“…A previous Ontario study found 1.8 heart failure events that required hospitalization per 100 person-years among patients who received pertuzumab. 12 The percentage of patients who received pertuzumab and experienced cardiotoxicity-related adverse events in our study was similar to that in other studies, 10,16 which is also similar to the CLEOPATRA trial result of 3.8%. 15 The real-world definition of cardiotoxicityrelated adverse events we used was different from the definition used by the trial, which defined adverse events as more than a 10% point decline in left-ventricular ejection fraction at baseline, or to less than 50%, or if treatment was required.…”

Real-World Evidence of Trastuzumab, Pertuzumab, and Docetaxel Combination as a First-Line Treatment for Korean Patients with HER2-Positive Metastatic Breast Cancer

“…We analyzed the real-world, single center data from patients who underwent combination treatment with trastuzumab, pertuzumab, and docetaxel as a first-line chemotherapy for HER2positive MBC. Survival outcomes in this study were comparable to those of previous ones, including several studies using real-world data [12,[15][16][17]. In addition, in terms of ORR, our results were similar or better than those reported previously along with a higher CR rate of…”

“…All rights reserved. 17.9% [8,15]. Although safety outcomes in our study were consistent with those of previous studies, it should be considered that evaluation of toxicities was quite limited by the retrospective nature of this study.…”

Kinesin superfamily proteins: roles in osteosarcoma

“…This finding was significant. Some traditional chemo drugs based on microtubule targeting agents, such as taxol, are associated with severe side effects [87,88], since all cells, healthy and tumor cells, need microtubule functions. Therefore, a variety of Eg5 inhibitors have been developed, a certain of them have entered clinical trials, including Arry-520 (Sponsor: Array Biopharma) [ [104].…”