新辅助来曲唑和哌柏西利与第三代化疗用于高危雌激素受体阳性、人表皮生长因子受体2阴性乳腺癌患者后的生存结局
Survival outcomes after neoadjuvant letrozole and palbociclib versus third generation chemotherapy for patients with high-risk oestrogen receptor-positive HER2-negative breast cancer.
作者信息
Delaloge Suzette, Dureau Sylvain, D'Hondt Véronique, Desmoulins Isabelle, Heudel Pierre-Etienne, Duhoux Francois P, Levy Christelle, Lerebours Florence, Mouret-Reynier Marie A, Dalenc Florence, Frenel Jean-Sébastien, Jouannaud Christelle, Venat-Bouvet Laurence, Nguyen Suzanne, Callens Cécile, Gentien David, Rapinat Audrey, Manduzio Helene, Vincent-Salomon Anne, Lemonnier Jérôme, Cottu Paul
机构信息
Department of Cancer Medicine, Gustave Roussy, Villejuif, France.
Department of Biostatistics, Institut Curie, Paris, France.
出版信息
Eur J Cancer. 2022 May;166:300-308. doi: 10.1016/j.ejca.2022.01.014. Epub 2022 Mar 22.
BACKGROUND
Besides their development as additional adjuvant treatments, CDK4/6 inhibitors combined with endocrine therapy could represent less toxic alternatives to chemotherapy in postmenopausal women with high-risk oestrogen receptor-positive, HER2-negative breast cancer currently a candidate for chemotherapy. The multicentre, international, randomised phase 2 NEOPAL trial showed that the letrozole-palbociclib combination led to clinical and pathological responses equivalent to sequential anthracycline-taxanes chemotherapy. Secondary objectives included survival outcomes.
METHODS
Secondary end-points of NEOPAL included progression-free survival (PFS) and invasive-disease free survival (iDFS) in the intent-to-treat population. Exploratory end-points were overall survival (OS) and breast cancer specific survival (BCSS) in the intent-to-treat population, as well as iDFS, OS and BCSS according to the administration of chemotherapy.
RESULTS
Hundred and six patients were randomised. Pathological complete response rates were 3.8% and 5.9%. Twenty-three of the 53 patients in the letrozole-palbociclib arm received postoperative adjuvant chemotherapy. At a median follow-up of 40.4 months [0-56.6], 11 progressions have been observed, of which three were in the letrozole-palbociclib and 8 in the control arm. PFS (HR = 1.01; [95%CI 0.36-2.90], p = 0.98) and iDFS (HR = 0.83; [95%CI 0.31-2.23], p = 0.71) did not differ between both arms. The 40 months PFS rate was 86.7% [95%CI 78.0-96.4] and 89.9% [95%CI 81.8-98.7] in letrozole-palbociclib and control arms, respectively. Outcomes of patients who did not receive chemotherapy were not statistically different from those who received it.
CONCLUSIONS
NEOPAL suggests that a neoadjuvant letrozole-palbociclib strategy may allow sparing chemotherapy in some patients with luminal breast cancer while allowing good long-term outcomes. Larger confirmatory studies are needed.
背景
除了作为额外的辅助治疗手段进行研发外，对于目前适合化疗的高危雌激素受体阳性、人表皮生长因子受体2阴性的绝经后乳腺癌女性患者，CDK4/6抑制剂联合内分泌治疗可能是毒性低于化疗的替代方案。多中心、国际性、随机2期NEOPAL试验表明，来曲唑-帕博西尼联合治疗产生的临床和病理反应与序贯蒽环类-紫杉类化疗相当。次要目标包括生存结局。
方法
NEOPAL的次要终点包括意向性治疗人群的无进展生存期（PFS）和无侵袭性疾病生存期（iDFS）。探索性终点为意向性治疗人群的总生存期（OS）和乳腺癌特异性生存期（BCSS），以及根据化疗给药情况的iDFS、OS和BCSS。
结果
106例患者被随机分组。病理完全缓解率分别为3.8%和5.9%。来曲唑-帕博西尼组的53例患者中有23例接受了术后辅助化疗。在中位随访40.4个月[0 - 56.6]时，观察到11例疾病进展，其中3例在来曲唑-帕博西尼组，8例在对照组。两组之间的PFS（风险比[HR]=1.01；[95%置信区间（CI）0.36 - 2.90]，p = 0.98）和iDFS（HR = 0.83；[95%CI 0.31 - 2.23]，p = 0.71）无差异。来曲唑-帕博西尼组和对照组的40个月PFS率分别为86.7%[95%CI 78.0 - 96.4]和89.9%[95%CI 81.8 - 98.7]。未接受化疗的患者的结局与接受化疗的患者无统计学差异。
结论
NEOPAL研究表明，新辅助来曲唑-帕博西尼策略可能使部分管腔型乳腺癌患者免于化疗，同时获得良好的长期结局。需要开展更大规模的验证性研究。
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