Comparing efficacy and safety of P013, a proposed pertuzumab biosimilar, with the reference product in HER2-positive breast cancer patients: a randomized, phase III, equivalency clinical trial.

BACKGROUND: Breast cancer is the most frequently diagnosed cancer and the leading reason for cancer-related death among women. Neoadjuvant treatment with dual-HER2 (human epidermal growth factor receptor 2) blockade has shown promising effects in this regard. The present study aimed to compare the efficacy and safety of a proposed pertuzumab biosimilar with the reference pertuzumab. METHODS: This randomized, phase III, multicenter, equivalency clinical trial was conducted on chemotherapy-naive women with HER2-positive breast cancer. Patients were randomly assigned (1:1) to receive six cycles of either P013 (CinnaGen, Iran) or the originator product (Perjeta, Roche, Switzerland) along with trastuzumab, carboplatin, and docetaxel every 3 weeks. Patients were stratified by cancer type (operable, locally advanced, inflammatory) and hormone receptor status. The primary endpoint was breast pathologic complete response (bpCR). Secondary endpoints included comparisons of total pCR, overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity. RESULTS: Two hundred fourteen patients were randomized to treatment groups. bpCR rate in the per-protocol population was 67.62% in the P013 and 71.57% in the reference drug groups. Based on bpCR, P013 was equivalent to the reference pertuzumab with a mean difference of - 0.04 (95% CI: - 0.16, 0.09). Secondary endpoints were also comparable between the two groups. CONCLUSIONS: The proposed biosimilar P013 was equivalent to the reference product in terms of efficacy. The safety of both medications was also comparable.

Evaluation of Adherence to Antiemetic Treatment Guidelines in Patients With Chemotherapy-Induced Nausea and Vomiting in Teaching Hospitals in Tehran.

The present study evaluated adherence to antiemetic guidelines for prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in four tertiary university teaching hospitals in Tehran. This prospective observational study enrolled 382 adult patients on chemotherapy at oncology centers affiliated to medical universities located in Tehran. Patients were followed up during their chemotherapy cycles. Risk factors related to CINV were evaluated, and information on antiemetic prescribing patterns was gathered using direct interview and patient medical records. Guideline adherence was found to be low; however, 81.3% of the patients experienced chemotherapy without CINV. Low frequency of adherence to the guidelines in prescription patterns does not mean that prescription patterns were very different. Indeed, some drugs were added to base guideline recommendation regiments, since in high and moderate emetogenic chemotherapy categories, some novel antiemetics recommended by international guidelines are not yet included in Iranian pharmacopeia. It was shown that two drug classes were added as a common practice, namely, H1/H2 antagonists and dopamine receptor antagonist (metoclopramide). Statistically significant differences were found between antiemetic prescribing patterns of physicians and chemotherapy regimen category (aspect of emetogenic potential) (p < 0.001). The most commonly prescribed regimen in the minimal-emetic-risk category and the low-emetic-risk category was reported to be the combination of corticosteroids, 5HT3, and H1/H2 antagonists, 33% and 66.1% respectively. Moreover, corticosteroids +5HT3 and H1/H2 antagonists + NK1 antagonist were found to be the most frequently prescribed regimen in the moderate-emetic-risk category (39.7%) and high-emetic-risk category (41.8%). Antiemetic prescribing patterns were not completely compatible with the guidelines in moderate and high emetogenic chemotherapy categories. Differences were detected in two states of over- and undertreatment. The present study confirmed low level of adherence of antiemetic prescribing patterns with international guidelines. However, it could not be proved that high levels of adherence with the guidelines result in reduction of CINV incidence. Complete success in CINV control cannot be achieved only by adherence to the established guidelines as novel antiemetics recommended by the guidelines have not been included in the Iranian pharmacopeia as yet. The authors do recommend implementation of strategies for increasing guideline-compliant prescriptions with the aim of improving patients' outcomes. We also suggest that policymakers in healthcare system point more critically to overprescribing as an issue of concern.