Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
Juravinski Cancer Centre, Hamilton, Ontario, Canada.
Clin Cancer Res. 2020 Jun 1;26(11):2477-2486. doi: 10.1158/1078-0432.CCR-19-2576. Epub 2020 Jan 28.
The relevance of the MET/hepatocyte growth factor pathway in endometrial cancer tumor biology supports the clinical evaluation of cabozantinib in this disease.
PHL86/NCI#9322 (NCT01935934) is a single arm study that evaluated cabozantinib (60 mg once daily) in women with endometrial cancer with progression after chemotherapy. Coprimary endpoints were response rate and 12-week progression-free-survival (PFS). Patients with uncommon histology endometrial cancer (eg, carcinosarcoma and clear cell) were enrolled in a parallel exploratory cohort.
A total of 102 patients were accrued. Among 36 endometrioid histology patients, response rate was 14%, 12-week PFS rate was 67%, and median PFS was 4.8 months. In serous cohort of 34 patients, response rate was 12%, 12-week PFS was 56%, and median PFS was 4.0 months. In a separate cohort of 32 patients with uncommon histology endometrial cancer (including carcinosarcoma), response rate was 6% and 12-week PFS was 47%. Six patients were on treatment for >12 months, including two for >30 months. Common cabozantinib-related toxicities (>30% patients) included hypertension, fatigue, diarrhea, nausea, and hand-foot syndrome. Gastrointestinal fistula/perforation occurred in four of 70 (6%) patients with serous/endometrioid cancer and five of 32 (16%) patients in exploratory cohort. We observed increased frequency of responses with somatic mutation [four partial responses (PRs) in 10 patients, median PFS 7.6 months] and concurrent and mutations (three PRs in 12 patients, median PFS 5.9 months).
Cabozantinib has activity in serous and endometrioid histology endometrial cancer. These results support further evaluation in genomically characterized patient cohorts.
MET/肝细胞生长因子通路在子宫内膜癌肿瘤生物学中的相关性支持了卡博替尼在该疾病中的临床评估。
PHL86/NCI#9322（NCT01935934）是一项单臂研究，评估了卡博替尼（每日 60 毫克）在化疗后进展的子宫内膜癌女性中的疗效。主要终点是缓解率和 12 周无进展生存期（PFS）。罕见组织学类型的子宫内膜癌（如癌肉瘤和透明细胞癌）患者被纳入平行探索性队列。
共入组 102 例患者。在 36 例子宫内膜样组织学患者中，缓解率为 14%，12 周 PFS 率为 67%，中位 PFS 为 4.8 个月。在 34 例浆液性队列患者中，缓解率为 12%，12 周 PFS 为 56%，中位 PFS 为 4.0 个月。在另一组 32 例罕见组织学类型的子宫内膜癌（包括癌肉瘤）患者中，缓解率为 6%，12 周 PFS 为 47%。6 例患者的治疗时间超过 12 个月，其中 2 例超过 30 个月。常见的卡博替尼相关毒性（超过 30%的患者）包括高血压、疲劳、腹泻、恶心和手足综合征。胃肠瘘/穿孔发生在 70 例浆液性/子宫内膜样癌患者中的 4 例（6%）和探索性队列中的 32 例患者中的 5 例（16%）。我们观察到随着体细胞突变的增加，反应频率增加[10 例患者中有 4 例部分缓解（PR），中位 PFS 为 7.6 个月]，同时 和 突变也增加（12 例患者中有 3 例 PR，中位 PFS 为 5.9 个月）。
卡博替尼在浆液性和子宫内膜样组织学子宫内膜癌中有活性。这些结果支持在基因组特征化的患者队列中进一步评估。
