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Results from the PHERGain phase 2 randomized trial, recently published on The Lancet, show the feasibility, safety and efficacy of a chemotherapy de-escalation strategy based on 18fluorine-fluorodeoxyglucose-PET and adapted to pathological complete response in patients with HER2+ early breast cancer.
PHERGain was a randomized, open-label, phase 2 trial that took place in 45 hospitals in seven European countries, involving 356 patients with centrally confirmed, HER2+, stage I–IIIA invasive, operable breast cancer with at least one PET-evaluable lesion. Participants were randomly allocated in a 1:4 ratio to either group A (71 patients) receiving docetaxel, carboplatin, trastuzumab and pertuzumab (TCHP), or group B (285 patients), receiving trastuzumab and pertuzumab with or without endocrine therapy, every 3 weeks. A PET was conducted at baseline and after 2 treatment cycles: patients in group B who were PET-responders continued with trastuzumab and pertuzumab with or without endocrine therapy for six cycles, while PET-non-responders were switched to receive six cycles of TCHP. After surgery, patients in group B who were PET-responders who did not achieve a pCR received six cycles of TCHP. At a median follow-up of 43,3 months, the 3-year invasive disease-free survival rate of group B was 94,8%, with treatment-related adverse events and serious adverse events numerically higher in patients of group A than of group B. «Multiple clinical studies have confirmed that the pCR after neoadjuvant chemotherapy is a reliable surrogate endpoint to predict long-term outcomes in patients with early breast cancer», authors write. «Different studies have also demonstrated encouraging antitumor activity in terms of pCR in HER2-positive patients exclusively treated with dual HER2 blockade. In addition, an early metabolic evaluation using 18F-FDG-PET could help to define which patients with HER2-positive tumors have an increased probability of reaching a pCR to chemotherapy-free regimens. PHERGain is the first study evaluating an individualized 18F-FDG-PET-based, pCR-adapted strategy that permits patients who are sensitive to exclusive neoadjuvant treatment with trastuzumab and pertuzumab to completely skip chemotherapy», authors continue. «This study shows that the 3-year invasive disease-free survival from surgery with an innovative de-escalating approach was excellent, despite omitting chemotherapy in around one third of the patients. Outstanding 3-year outcomes were also observed in the subgroup of patients who obtained a pCR response with trastuzumab and pertuzumab and therefore never received chemotherapy. This de-escalation approach enables a significant reduction of toxicity for this specific patient population».
Results from the PHERGain phase 2 randomized trial, recently published on The Lancet, show the feasibility, safety and efficacy of a chemotherapy de-escalation strategy based on 18fluorine-fluorodeoxyglucose-PET and adapted to pathological complete response in patients with HER2+ early breast cancer.
PHERGain was a randomized, open-label, phase 2 trial that took place in 45 hospitals in seven European countries, involving 356 patients with centrally confirmed, HER2+, stage I–IIIA invasive, operable breast cancer with at least one PET-evaluable lesion. Participants were randomly allocated in a 1:4 ratio to either group A (71 patients) receiving docetaxel, carboplatin, trastuzumab and pertuzumab (TCHP), or group B (285 patients), receiving trastuzumab and pertuzumab with or without endocrine therapy, every 3 weeks. A PET was conducted at baseline and after 2 treatment cycles: patients in group B who were PET-responders continued with trastuzumab and pertuzumab with or without endocrine therapy for six cycles, while PET-non-responders were switched to receive six cycles of TCHP. After surgery, patients in group B who were PET-responders who did not achieve a pCR received six cycles of TCHP. At a median follow-up of 43,3 months, the 3-year invasive disease-free survival rate of group B was 94,8%, with treatment-related adverse events and serious adverse events numerically higher in patients of group A than of group B. «Multiple clinical studies have confirmed that the pCR after neoadjuvant chemotherapy is a reliable surrogate endpoint to predict long-term outcomes in patients with early breast cancer», authors write. «Different studies have also demonstrated encouraging antitumor activity in terms of pCR in HER2-positive patients exclusively treated with dual HER2 blockade. In addition, an early metabolic evaluation using 18F-FDG-PET could help to define which patients with HER2-positive tumors have an increased probability of reaching a pCR to chemotherapy-free regimens. PHERGain is the first study evaluating an individualized 18F-FDG-PET-based, pCR-adapted strategy that permits patients who are sensitive to exclusive neoadjuvant treatment with trastuzumab and pertuzumab to completely skip chemotherapy», authors continue. «This study shows that the 3-year invasive disease-free survival from surgery with an innovative de-escalating approach was excellent, despite omitting chemotherapy in around one third of the patients. Outstanding 3-year outcomes were also observed in the subgroup of patients who obtained a pCR response with trastuzumab and pertuzumab and therefore never received chemotherapy. This de-escalation approach enables a significant reduction of toxicity for this specific patient population».
