Approximately 40% of hormone receptor-positive (HR⁺), HER2-negative (HER2^–) breast cancers harbour activating mutations in PIK3CA (encoding the catalytic subunit of PI3Kα); these mutations are generally associated with a poor prognosis but also responsiveness to inhibitors of the PI3K–AKT pathway. Now, data from the phase III INAVO120 trial demonstrate that addition of the selective PI3Kα inhibitor and degrader inavolisib to standard-of-care first-line endocrine plus CDK4/6 inhibitor therapy for advanced-stage disease is feasible and increases efficacy.

In INAVO120, 325 patients with metastatic recurrence of PIK3CA-mutant HR⁺, HER2^– breast cancer during, or within 12 months of completing, adjuvant endocrine-based therapy were randomly assigned (1:1) to receive palbociclib and fulvestrant plus either inavolisib or placebo. The requirement for early disease relapse enriched for patients with a poor prognosis: 83% had received chemotherapy, 80% had visceral metastases, 52% had liver metastases and 51% had ≥3 metastases. Notably, however, only 1% of patients had received a CDK4/6 inhibitor as part of adjuvant therapy. Progression-free survival (PFS) was the primary end point.

大约 40% 的激素受体阳性 （HR⁺）、HER2 阴性 （HER2^–） 乳腺癌在 PIK3CA（编码 PI3Kα 的催化亚基）中携带激活突变;这些突变通常与不良预后有关，但也与对 PI3K-AKT 通路抑制剂的反应有关。现在，来自 III 期 INAVO120 试验的数据表明，将选择性 PI3Kα 抑制剂和降解剂 inavolisib 添加到晚期疾病的标准一线内分泌加 CDK4/6 抑制剂治疗中是可行的，并且可以提高疗效。

在 INAVO120 中，325 例 PIK3CA 突变 HR⁺、HER2^– 乳腺癌转移复发的患者在完成辅助内分泌治疗期间或完成后 12 个月内被随机分配 （1：1） 接受 palbociclib 和氟维司群加 inavolisib 或安慰剂。预后不良患者早期疾病复发的要求丰富： 83% 接受化疗，80% 有内脏转移，52% 有肝转移，51% 有 ≥3 个转移。然而，值得注意的是，只有 1% 的患者接受了 CDK4/6 抑制剂作为辅助治疗的一部分。无进展生存期 （PFS） 是主要终点。