Therapeutic Advances in Medical Oncology (Nov 2021)

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

  • Laura Pizzuti,
  • Eriseld Krasniqi,
  • Isabella Sperduti,
  • Maddalena Barba,
  • Teresa Gamucci,
  • Maria Mauri,
  • Enzo Maria Veltri,
  • Icro Meattini,
  • Rossana Berardi,
  • Francesca Sofia Di Lisa,
  • Clara Natoli,
  • Mirco Pistelli,
  • Laura Iezzi,
  • Emanuela Risi,
  • Nicola D’Ostilio,
  • Silverio Tomao,
  • Corrado Ficorella,
  • Katia Cannita,
  • Ferdinando Riccardi,
  • Alessandra Cassano,
  • Emilio Bria,
  • Maria Agnese Fabbri,
  • Marco Mazzotta,
  • Giacomo Barchiesi,
  • Andrea Botticelli,
  • Giuliana D’Auria,
  • Anna Ceribelli,
  • Andrea Michelotti,
  • Antonio Russo,
  • Beatrice Taurelli Salimbeni,
  • Giuseppina Sarobba,
  • Francesco Giotta,
  • Ida Paris,
  • Rosa Saltarelli,
  • Daniele Marinelli,
  • Domenico Corsi,
  • Elisabetta Maria Capomolla,
  • Valentina Sini,
  • Luca Moscetti,
  • Lucia Mentuccia,
  • Giuseppe Tonini,
  • Mimma Raffaele,
  • Luca Marchetti,
  • Mauro Minelli,
  • Enzo Maria Ruggeri,
  • Paola Scavina,
  • Olivia Bacciu,
  • Nello Salesi,
  • Lorenzo Livi,
  • Nicola Tinari,
  • Antonino Grassadonia,
  • Angelo Fedele Scinto,
  • Rosalinda Rossi,
  • Maria Rosaria Valerio,
  • Elisabetta Landucci,
  • Simonetta Stani,
  • Beatrice Fratini,
  • Marcello Maugeri-Saccà,
  • Michele De Tursi,
  • Angela Maione,
  • Daniele Santini,
  • Armando Orlandi,
  • Vito Lorusso,
  • Enrico Cortesi,
  • Giuseppe Sanguineti,
  • Paola Pinnarò,
  • Federico Cappuzzo,
  • Lorenza Landi,
  • Claudio Botti,
  • Federica Tomao,
  • Sonia Cappelli,
  • Giulia Bon,
  • Fabio Pelle,
  • Flavia Cavicchi,
  • Elena Fiorio,
  • Jennifer Foglietta,
  • Simone Scagnoli,
  • Paolo Marchetti,
  • Gennaro Ciliberto,
  • Patrizia Vici

DOI
https://doi.org/10.1177/17588359211059873
Journal volume & issue
Vol. 13

Abstract

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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.