PANHER study: a 20-year treatment outcome analysis from a multicentre observational study of HER2-positive advanced breast cancer patients from the real-world setting. (November 2021)

• Record Type: Journal Article
• Authors: Pizzuti, Laura; Krasniqi, Eriseld; Sperduti, Isabella; Barba, Maddalena; Gamucci, Teresa; Mauri, Maria; Veltri, Enzo Maria; Meattini, Icro; Berardi, Rossana; Di Lisa, Francesca Sofia; Natoli, Clara; Pistelli, Mirco; Iezzi, Laura; Risi, Emanuela; D'Ostilio, Nicola; Tomao, Silverio; Ficorella, Corrado; Cannita, Katia; Riccardi, Ferdinando; Cassano, Alessandra; Bria, Emilio; Fabbri, Maria Agnese; Mazzotta, Marco; Barchiesi, Giacomo; Botticelli, Andrea; D'Auria, Giuliana; Ceribelli, Anna; Michelotti, Andrea; Russo, Antonio; Salimbeni, Beatrice Taurelli; Sarobba, Giuseppina; Giotta, Francesco; Paris, Ida; Saltarelli, Rosa; Marinelli, Daniele; Corsi, Domenico; Capomolla, Elisabetta Maria; Sini, Valentina; Moscetti, Luca; Mentuccia, Lucia; Tonini, Giuseppe; Raffaele, Mimma; Marchetti, Luca; Minelli, Mauro; Ruggeri, Enzo Maria; Scavina, Paola; Bacciu, Olivia; Salesi, Nello; Livi, Lorenzo; Tinari, Nicola; Grassadonia, Antonino; Fedele Scinto, Angelo; Rossi, Rosalinda; Valerio, Maria Rosaria; Landucci, Elisabetta; Stani, Simonetta; Fratini, Beatrice; Maugeri-Saccà, Marcello; De Tursi, Michele; Maione, Angela; Santini, Daniele; Orlandi, Armando; Lorusso, Vito; Cortesi, Enrico; Sanguineti, Giuseppe; Pinnarò, Paola; Cappuzzo, Federico; Landi, Lorenza; Botti, Claudio; Tomao, Federica; Cappelli, Sonia; Bon, Giulia; Pelle, Fabio; Cavicchi, Flavia; Fiorio, Elena; Foglietta, Jennifer; Scagnoli, Simone; Marchetti, Paolo; Ciliberto, Gennaro; Vici, Patrizia;
• Is Part Of: Therapeutic advances in medical oncology. Volume 13(2021)
• Publication Date: 2021-11
• Subjects: advanced breast cancer -- HER2-positive -- lapatinib -- pertuzumab -- sequence -- T-DM1; Oncology -- Periodicals; Cancer -- Treatment -- Periodicals; 616.994005
• DOI: 10.1177/17588359211059873
• Languages: English
• ISSNs: 1758-8340

Abstract

Background: The evolution of therapeutic landscape of human epidermal growth factor receptor-2 (HER2)-positive breast cancer (BC) has led to an unprecedented outcome improvement, even if the optimal sequence strategy is still debated. To address this issue and to provide a picture of the advancement of anti-HER2 treatments, we performed a large, multicenter, retrospective study of HER2-positive BC patients. Methods: The observational PANHER study included 1, 328 HER2-positive advanced BC patients treated with HER2 blocking agents since June 2000 throughout July 2020. Endpoints of efficacy were progression-free survival (PFS) and overall survival (OS). Results: Patients who received a first-line pertuzumab-based regimen showed better PFS ( p < 0.0001) and OS ( p = 0.004) than those receiving other treatments. Median PFS and mOS from second-line starting were 8 and 28 months, without significant differences among various regimens. Pertuzumab-pretreated patients showed a mPFS and a mOS from second-line starting not significantly affected by type of second line, that is, T-DM1 or lapatinib/capecitabine ( p = 0.80 and p = 0.45, respectively). Conversely, pertuzumab-naïve patients receiving second-line T-DM1 showed a significantly higher mPFS compared with that of patients treated with lapatinib/capecitabine ( p = 0.004). Median OS from metastatic disease diagnosis was higher in patients treated with trastuzumab-based first line followed by second-line T-DM1 in comparison to pertuzumab-based first-line and second-line T-DM1 ( p = 0.003), although these data might be partially influenced by more favorable prognostic characteristics of patients in the pre-pertuzumab era . No significant differences emerged when comparing patients treated with 'old' or 'new' drugs ( p = 0.43), even though differences in the length of the follow-up between the two cohorts should be taken into account. Conclusion: Our results confirmed a relevant impact of first-line pertuzumab-based treatment and showed lower efficacy of second-line T-DM1 in trastuzumab/pertuzumab pretreated, as compared with pertuzumab-naïve patients. Our findings may help delineate a more appropriate therapeutic strategy in HER2-positive metastatic BC. Prospective randomized trials addressing this topic are awaited.