Pathologic response and survival after neoadjuvant chemotherapy with or without pertuzumab in patients with HER2-positive breast cancer: the Neopearl nationwide collaborative study

Agnese Fabbri; Fabrizio Nelli; Andrea Botticelli; Diana Giannarelli; Eleonora Marrucci; Cristina Fiore; Antonella Virtuoso; Simone Scagnoli; Simona Pisegna; Daniele Alesini; Valentina Sini; Armando Orlandi; Alessandra Fabi; Federico Piacentini; Luca Moscetti; Giuliana D'Auria; Teresa Gamucci; Marco Mazzotta; Laura Pizzuti; Patrizia Vici; Elisabetta Cretella; Paola Scavina; Annalisa La Cesa; Mara Persano; Francesco Atzori; Enzo Maria Ruggeri

doi:10.3389/fonc.2023.1177681

Pathologic response and survival after neoadjuvant chemotherapy with or without pertuzumab in patients with HER2-positive breast cancer: the Neopearl nationwide collaborative study

Front Oncol. 2023 Jun 27:13:1177681. doi: 10.3389/fonc.2023.1177681. eCollection 2023.

Authors

Agnese Fabbri¹, Fabrizio Nelli¹, Andrea Botticelli², Diana Giannarelli³, Eleonora Marrucci¹, Cristina Fiore¹, Antonella Virtuoso¹, Simone Scagnoli², Simona Pisegna², Daniele Alesini⁴, Valentina Sini⁴, Armando Orlandi⁵, Alessandra Fabi⁶, Federico Piacentini⁷, Luca Moscetti⁷, Giuliana D'Auria⁸, Teresa Gamucci⁸, Marco Mazzotta⁸, Laura Pizzuti⁹, Patrizia Vici⁹, Elisabetta Cretella¹⁰, Paola Scavina¹¹, Annalisa La Cesa¹², Mara Persano¹³, Francesco Atzori¹³, Enzo Maria Ruggeri¹

Affiliations

¹ Department of Oncology and Hematology, Medical Oncology and Breast Unit, Central Hospital of Belcolle, Viterbo, Italy.
² Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, Rome, Italy.
³ Biostatistics Unit, Scientific Directorate, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.
⁴ UOSD Centro Oncologico S. Spirito e Nuovo Regina Margherita (SS-NRM), Ospedale Santo Spirito in Sassia, Rome, Italy.
⁵ Department of Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
⁶ Precision Medicine Breast Unit, Scientific Directorate, Department of Women, Children and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
⁷ Department of Medical Oncology, University Hospital of Modena, Modena, Italy.
⁸ Department of Medical Oncology, Medical Oncology Unit, Sandro Pertini Hospital, Rome, Italy.
⁹ UOSD Sperimentazioni di fase IV, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
¹⁰ Department of Medical Oncology, Medical Oncology Unit, Ospedale Di Bolzano, Azienda Sanitaria Alto Adige, Bolzano, Italy.
¹¹ Department of Medical Oncology, Medical Oncology Unit, San Giovanni Addolorata Hospital, Rome, Italy.
¹² Department of Medical Oncology, Campus Bio-Medico University, Rome, Italy.
¹³ Department of Medical Oncology, University Hospital and University of Cagliari, Cagliari, Italy.

Abstract

Purpose: Clinical trials have shown a significant increase in pathologic complete response (pCR) with the addition of pertuzumab to neoadjuvant chemotherapy for patients with early-stage HER-2 positive breast cancer. To date, limited studies have examined comparative outcomes of neoadjuvant pertuzumab in real-world setting. The Neopearl study aimed to assess comparative real-life efficacy and safety of neoadjuvant pertuzumab for these patients.

Methods: We conducted a nationwide retrospective analysis involving 17 oncology facilities with a certified multidisciplinary breast cancer treatment committee. We identified patients with HER-2 positive stage II-III breast cancer treated with neoadjuvant chemotherapy based on trastuzumab and taxanes with or without pertuzumab. All patients underwent breast surgery and received a comprehensive cardiologic evaluation at baseline and after neoadjuvant treatment. Patients who received the combination of pertuzumab, trastuzumab, and chemotherapy constituted case cohort (PTCT), whereas those treated with trastuzumab and chemotherapy accounted for control cohort (TCT). The pCR rate and 5-year event free survival (EFS) were the primary outcomes. Secondary end-points were rates of conversion from planned modified radical mastectomy (MRM) to breast conservation surgery (BCS) and cardiotoxicities.

Results: From March 2014 to April 2021, we included 271 patients, 134 (49%) and 137 (51%) in TCT and PTCT cohort, respectively. Positive axillary lymph nodes and stage III were more frequent in PTCT cohort. The pCR rate was significantly increased in patients who received pertuzumab (49% vs 62%; OR 1.74, 95%CI 1.04-2.89) and with HER-2 enriched subtypes (16% vs 85%; OR 2.94, 95%CI 1.60-5.41). After a median follow-up of 5 years, the 5-year EFS was significantly prolonged only in patients treated with pertuzumab (81% vs 93%; HR 2.22, 95%CI 1.03-4.79). The same analysis performed on propensity score matched population showed concordant results. On univariate analysis, only patients with positive lymph nodes were found to benefit from pertuzumab for both pCR and 5-year EFS. The rates of conversion from MRM to BCS and cardiologic toxicities did not differ between the cohorts.

Conclusion: Our findings support previous data on improved outcomes with the addition of pertuzumab to trastuzumab-based neoadjuvant chemotherapy. This benefit seems to be more significant in patients with clinically positive lymph nodes.

Keywords: HER-2 positive; breast cancer; neoadjuvant chemotherapy; pertuzumab; real-world data; trastuzumab.

Copyright © 2023 Fabbri, Nelli, Botticelli, Giannarelli, Marrucci, Fiore, Virtuoso, Scagnoli, Pisegna, Alesini, Sini, Orlandi, Fabi, Piacentini, Moscetti, D’Auria, Gamucci, Mazzotta, Pizzuti, Vici, Cretella, Scavina, La Cesa, Persano, Atzori and Ruggeri.