US Food and Drug Administration Approval Summary: Inavolisib With Palbociclib and Fulvestrant for Endocrine-Resistant, PIK3CA-Mutated, Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, Locally Advanced or Metastatic Breast Cancer.

patients_and_methods

Approval was based on INAVO120, a randomized, double-blind, placebo-controlledtrial in 325 patients with endocrine-resistant, PIK3CA-mutated, hormone receptor-positive, HER2-negative, locally advanced or MBC.

该批准基于INAVO120试验，这是一项随机、双盲、安慰剂对照试验，涉及325名内分泌抵抗性、PIK3CA突变、激素受体阳性、HER2阴性的局部晚期或MBC患者。

Patients were randomly assigned (1:1) to either inavolisib (n = 161) or placebo (n = 164) in combination with palbociclib and fulvestrant.

患者被随机分配（1:1）至 either inavolisib（n = 161）或安慰剂（n = 164），与 palbociclib 和 fulvestrant 联合使用。

Results

INAVO120 met its primary end point of progression-free survival(PFS) by investigator assessment, with a median PFS of 15.0 months for inavolisib + palbociclib + fulvestrant versus 7.3 months for placebo + palbociclib + fulvestrant (hazard ratio[HR], 0.43 [95% CI, 0.32 to 0.59]; P < .0001).

INAVO120 达到了其主要终点，即无进展生存期（PFS），通过研究者评估，inavolisib + palbociclib + fulvestrant 的中位无进展生存期为 15.0 个月，而安慰剂 + palbociclib + fulvestrant 的中位无进展生存期为 7.3 个月（风险比 [HR], 0.43 [95% 置信区间, 0.32 到 0.59]; P < .0001）。

The objective response ratewas 58% (95% CI, 50 to 66) versus 25% (95% CI, 19 to 32).

客观缓解率为58%（95% CI，50至66）对比25%（95% CI，19至32）。

The median duration of response was 18.4 months (95% CI, 10.4 to 22.2) versus 9.6 months (95% CI, 7.4 to 16.6).

反应持续时间的中位数为18.4个月（95% CI，10.4至22.2）对比9.6个月（95% CI，7.4至16.6）。

Interim analysis of overall survivaldid not reach statistical significance but was supportive of the overall benefit-risk assessment with a HR of 0.64 (95% CI, 0.43 to 0.97).

中期总生存分析未达到统计学显著性，但支持整体获益-风险评估，风险比为0.64（95%置信区间，0.43至0.97）。

Consistent with the PI3Kα inhibitor class, common adverse reactions noted with inavolisib included hyperglycemia, stomatitis, diarrhea, and rash.

与PI3Kα抑制剂类药物一致，inavolisib常见的不良反应包括高血糖、口腔炎、腹泻和皮疹。

Conclusions

The approval of inavolisib with palbociclib plus fulvestrant was based on a statistically significant and clinically meaningful improvement in PFS observed in the INAVO120 trial. Before this approval, there were no specific therapies approved by the FDA for the first-line treatment of patients with endocrine-resistant, hormone receptor-positive advanced or MBC.

基于INAVO120试验中观察到的无进展生存期（PFS）的统计学上显著且具有临床意义的改善，inavolisib与palbociclib加fulvestrant的批准得以实现。