Coudert Bruno, Pierga Jean-Yves, Mouret-Reynier Marie-Ange, Kerrou Kaldoun, Ferrero Jean-Marc, Petit Thierry, Du Fanny Le, Dupré Pierre-François, Bachelot Thomas, Gabelle Philippe, Chauvet Marie-Pierre, Coeffic David, Barbe Catherine, Prevost Jean-Briac, Paintaud Gilles, Thibault Gilles, Ferhat Abdennour, Dupin Julien, Berriolo-Riedinger Alina, Arnould Laurent
Centre Georges-Francois Leclerc, Dijon, France.
Institut Curie, Université de Paris, Paris, France.
EClinicalMedicine. 2020 Nov 4;28:100566. doi: 10.1016/j.eclinm.2020.100566. eCollection 2020 Nov.
The open-label, randomised Phase 2 AVATAXHER study (NCT01142778) demonstrated that early PET assessment identified HER2-positive breast cancer patients who responded poorly to neoadjuvant docetaxel plus trastuzumab. Adding neoadjuvant bevacizumab for PET-predicted poor-responders improved pathological complete response (pCR) rates (43.8% vs 24.0%). We investigated long-term study outcomes.
Patients were treated in three groups. All patients initially received two cycles of standard neoadjuvant therapy with [¹⁸F]-FDG PET conducted before each cycle. Those with ≥70% change in the maximum standardised uptake value (∆SUVmax) received four further cycles of standard neoadjuvant therapy (PET responders). PET-predicted poor-responders (∆SUVmax <70%) were randomised (2:1) to neoadjuvant therapy with (Group A) or without (Group B) bevacizumab for cycles 3-6. All patients received one further cycle of trastuzumab before surgery plus adjuvant trastuzumab (11 cycles).
142 patients were randomized and treated (PET responders, = 69; Group A, = 48; Group B, = 25). 5-year disease-free survival rates were 90.5% (95% CI: 80.0-95.6%) in PET responders, 90.2% (95% CI: 75.9-96.2%) in Group A, and 76.0% (95% CI: 54.2-88.4%) in Group B. However, no difference was observed between randomised arms in a sensitivity analysis. During adjuvant therapy, the incidence of Grade ≥3 (Group A: 25.6%; Group B 12.5%) and serious adverse events (Group A: 18.6%; Group B 12.5%) was higher in Group A vs Group B, but with no apparent effect on cardiac events.
In patients with HER2-positive breast cancer, an intervention based on early PET assessment and improvement of pCR does not modify disease-free survival.
Roche France.
开放标签的随机2期AVATAXHER研究（NCT01142778）表明，早期PET评估可识别出对新辅助多西他赛加曲妥珠单抗反应不佳的HER2阳性乳腺癌患者。对于PET预测的反应不佳者，添加新辅助贝伐单抗可提高病理完全缓解（pCR）率（43.8%对24.0%）。我们调查了长期研究结果。
患者分为三组进行治疗。所有患者最初接受两个周期的标准新辅助治疗，每个周期前进行[¹⁸F]-FDG PET检查。最大标准化摄取值（∆SUVmax）变化≥70%的患者再接受四个周期的标准新辅助治疗（PET反应者）。PET预测的反应不佳者（∆SUVmax<70%）被随机分配（2:1）接受第3至6周期含（A组）或不含（B组）贝伐单抗的新辅助治疗。所有患者在手术前再接受一个周期的曲妥珠单抗治疗以及辅助曲妥珠单抗治疗（共11个周期）。
142例患者被随机分组并接受治疗（PET反应者，n = 69；A组，n = 48；B组，n = 25）。PET反应者的5年无病生存率为90.5%（95%CI：80.0 - 95.6%），A组为90.2%（95%CI：75.9 - 96.2%），B组为76.0%（95%CI：54.2 - 88.4%）。然而，在敏感性分析中，随机分组的各治疗组之间未观察到差异。在辅助治疗期间，A组3级及以上不良事件（A组：25.6%；B组12.5%）和严重不良事件（A组：18.6%；B组12.5%）的发生率高于B组，但对心脏事件无明显影响。
在HER2阳性乳腺癌患者中，基于早期PET评估和提高pCR的干预措施并不能改变无病生存率。
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