Daniele Rossini1, Marco Maria Germani1, Filippo Pagani2, Antonio Pellino3, Emanuela Dell'Aquila4, Maria Bensi5, Nicole Liscia6, Roberto Moretto1, Alessandra Boccaccino1, Michele Prisciandaro2, Sara Manglaviti2, Marta Schirripa7, Raffaella Vivolo5, Mario Scartozzi6, Daniele Santini4, Lisa Salvatore5, Filippo Pietrantonio2, Fotios Loupakis7, Alfredo Falcone1, Chiara Cremolini8. 1. Department of Translational Research and New Technologies in Medicine and Surgery, Unit of Medical Oncology 2, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy. 2. Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 3. Unit of Medical Oncology 1, Department of Clinical and Experimental Oncology, Veneto Institute of Oncology, IOV-IRCCS, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy. 4. Department of Medical Oncology, Campus Bio-Medico, University of Rome, Rome, Italy. 5. Fondazione Policlinico Universitario A. Gemelli, IRCCS-UOC Oncologia Medica, Rome, Italy. 6. Medical Oncology Department, University Hospital, University of Cagliari, Cagliari, Italy. 7. Unit of Medical Oncology 1, Department of Clinical and Experimental Oncology, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy. 8. Department of Translational Research and New Technologies in Medicine and Surgery, Unit of Medical Oncology 2, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy. Electronic address: chiaracremolini@gmail.com.
Abstract
BACKGROUND: On the basis of retrospective analyses and phase 2 studies, metastatic colorectal cancer patients whose disease responded to a first-line regimen containing an anti-epidermal growth factor receptor (EGFR) agent may experience benefit from anti-EGFR readministration in later therapy lines. While the analysis of circulating tumor DNA seems a promising tool to select the best candidates for this strategy, identifying clinical predictors of anti-EGFR sensitivity would be useful to drive treatment choices in daily practice. PATIENTS AND METHODS: A real-life database of 5530 patients treated at 6 institutions was queried. Included were patients who were retreated with anti-EGFRs, who had RAS/BRAF wild-type-status tissue samples, who had received a first-line anti-EGFR-based regimen with at least stable disease as best response, and who had received at least one further line of therapy before anti-EGFR retreatment. The association with overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of variables potentially related to anti-EGFR sensitivity was investigated. RESULTS: A total of 86 patients were identified. The ORR during anti-EGFR retreatment was 19.8%; median PFS and OS were 3.8 and 10.2 months, respectively. No significant association of clinical features of anti-EGFR sensitivity with ORR, PFS, and OS was observed. Among the 56 patients with a time from the last anti-EGFR administration to first-line progressive disease of < 3 months (rechallenge group), > 2 prior therapy lines and a longer anti-EGFR-free interval were associated with higher ORR, but not with longer PFS or OS. CONCLUSION: Clinical features we deemed surrogates of anti-EGFR sensitivity were not reliable predictors of benefit from anti-EGFR retreatment.
BACKGROUND: On the basis of retrospective analyses and phase 2 studies, metastatic colorectal cancerpatients whose disease responded to a first-line regimen containing an anti-epidermal growth factor receptor (EGFR) agent may experience benefit from anti-EGFR readministration in later therapy lines. While the analysis of circulating tumor DNA seems a promising tool to select the best candidates for this strategy, identifying clinical predictors of anti-EGFR sensitivity would be useful to drive treatment choices in daily practice. PATIENTS AND METHODS: A real-life database of 5530 patients treated at 6 institutions was queried. Included were patients who were retreated with anti-EGFRs, who had RAS/BRAF wild-type-status tissue samples, who had received a first-line anti-EGFR-based regimen with at least stable disease as best response, and who had received at least one further line of therapy before anti-EGFR retreatment. The association with overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of variables potentially related to anti-EGFR sensitivity was investigated. RESULTS: A total of 86 patients were identified. The ORR during anti-EGFR retreatment was 19.8%; median PFS and OS were 3.8 and 10.2 months, respectively. No significant association of clinical features of anti-EGFR sensitivity with ORR, PFS, and OS was observed. Among the 56 patients with a time from the last anti-EGFR administration to first-line progressive disease of < 3 months (rechallenge group), > 2 prior therapy lines and a longer anti-EGFR-free interval were associated with higher ORR, but not with longer PFS or OS. CONCLUSION: Clinical features we deemed surrogates of anti-EGFR sensitivity were not reliable predictors of benefit from anti-EGFR retreatment.
Authors: Martin S Schulz; Sebastian Wolf; Vera Struck; Niklas Thomas; Gabriele Husman; Stefan Zeuzem; Christine Koch; Jörg Trojan; Andreas Anton Schnitzbauer; Wolf Otto Bechstein; Oliver Waidmann Journal: Cancers (Basel) Date: 2022-03-24 Impact factor: 6.639