Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia

Abstract

Prospective assessment of treatments known to benefit patients in global clinical trials in specific racial groups is essential.OBJECTIVE To compare the efficacy, safety, and tolerability of adding pertuzumab to trastuzumab and docetaxel vs placebo, trastuzumab, and docetaxel in Asian patients with ERBB2-positive early or locally advanced breast cancer. DESIGN, SETTING, AND PARTICIPANTSThis multicenter, double-blind, placebo-controlled phase 3 trial enrolled 329 women with ERBB2-positive early (T2-3, N0-1, M0) or locally advanced breast cancer (T2-3, N2 or N3, M0; T4, any N, M0) and primary tumor larger than 2 cm from March 14, 2016, to March 13, 2017. Analysis of the primary end point was performed on an intention-to-treat basis.INTERVENTIONS Before surgery, patients received 4 cycles of intravenous pertuzumab (840-mg loading dose and 420-mg maintenance doses), trastuzumab (8-mg/kg loading dose and 6-mg/kg maintenance doses), and docetaxel (75 mg/m 2 ) or intravenous placebo, trastuzumab, and docetaxel every 3 weeks. After surgery, patients received 3 cycles of intravenous fluorouracil, epirubicin, and cyclophosphamide followed by 13 cycles of the same intravenous anti-ERBB2 therapy (pertuzumab and trastuzumab or placebo and trastuzumab) for up to 1 year. MAIN OUTCOMES AND MEASURESThe primary end point was independent review committee-assessed total pathologic complete response rate. The 2-sided Cochran-Mantel-Haenszel test, stratified by disease category and hormone receptor status, was used to compare rates between treatment groups.RESULTS In total, 329 female patients were randomized (pertuzumab, 219; and placebo, 110; mean [SD] age, 48.8 [9.5] years). In the intention-to-treat population, total pathologic complete response rates were 39.3% (86 of 219) in the pertuzumab group and 21.8% (24 of 110) in the placebo group (difference, 17.5% [95% CI, 6.9%-28.0%]; P = .001). Of the most common grade 3 or higher adverse events, there was a higher incidence of neutropenia in the pertuzumab group (83 of 218 [38.1%] vs 36 of 110 [32.7%]). Serious adverse events were reported in 10.1% of patients (22 of 218) in the pertuzumab group and 8.2% of patients (9 of 110) in the placebo group.CONCLUSIONS AND RELEVANCE Treatment with pertuzumab, trastuzumab, and docetaxel resulted in a statistically significant improvement in the total pathologic complete response rate vs placebo, trastuzumab, and docetaxel for the neoadjuvant treatment of ERBB2-positive early or locally advanced breast cancer in Asian patients. Safety data were in line with the known pertuzumab safety profile and generally comparable between treatment groups. The PEONY trial adds to the totality of data showing the benefit of the pertuzumab regimen.

Dual HER-2 blockade therapy increases the risk of developing cardiac toxicities in HER-2 positive breast cancer: an up-to-date comprehensive meta-analysis

“…Table 1 listed the baseline characteristics of patients and studies. The quality of each included study was roughly assessed according to Jadad scale, four trials [16,21,34,37] were doubleblind, placebo-controlled trials, thus had a Jadad score of 5, and the remaining eleven trials were open-label controlled trials, thus had a Jadad score of 3.…”

“…There were 302 LVEF decline events among these patients. The highest incidence (8.7%; 95% CI 5.3% to 13.9%) was observed in a phase III breast cancer neoadjuvant trial of trastuzumab plus lapatinib when concomitant with paclitaxel [22], while the lowest incidence was observed in four trials in which no events of LVEF decline occurred [16,27,31,37]. Using a random-effects model (χ2-based Q statistic test: Q= 31.75; p =0.004;I 2 = 55%), the summary incidence of LVEF decline in cancer patients treated with dual HER2 blockade was 4.6% (95% CI, 3.7% to 5.7%, figure 2A).…”

“…For LVEF decline associated with anti-HER2 monotherapy, the highest incidence (13.4%; 95% CI 10.2% to 17.4%) was observed in NSABP protocol B-41 trial [30], while no events of LVEF decline occurred in three trials [16,19,37]. Using a random-effects model (χ2-based Q statistic test: Q=108.33;p <0.001; I 2 =86%), the summary incidence of LVEF decline in cancer patients treated with anti-HER2 monotherapy was 3.2% (95% CI, 2.2% to 4.6%, figure 2B).…”

<p>Trastuzumab with FLOT Regimen for the Perioperative Treatment of Resectable HER2 + Advanced Gastric Cancer: A Retrospective Study</p>

“…10 In HER2+ breast cancer, the addition of T to standard neoadjuvant chemotherapy significantly improved both, pathological complete response rates and event-free survival. 11 However, the question over whether the T in perioperative chemotherapy may further improve treatment outcomes in patients with localized or locally advanced resectable GC remains one of the major open questions in the current management of GC patients. Although a number of ongoing clinical studies have attempted to answer this question, the final results have not been reported.…”

“…5 A stage III ToGA clinical study showed that the efficacy of trastuzumab combined with an XP/FP regimen in patients with HER-2-positive advanced esophagogastric junction or gastric cancer was significantly better than that of patients receiving only chemotherapy. Median OS was 13.8 months (95% confidence interval [CI] [12][13][14][15][16] for patients assigned to the trastuzumab plus chemotherapy arm compared with 11.1 months (95% CI [10][11][12][13] in the chemotherapy group (hazard ratio [HR] 0.74; 95% CI 0.60--0.91; p = 0.0046). Especially in the patients with HER-2 immunohistochemistry 2 + and FISH positive or the patients with HER-2 immunohistochemistry 3 +, the survival improvement was more obvious, with the median OS better in the experimental arm (16.8 vs 11.8 months, HR: 0.65).…”