Phase II Trial of Cabozantinib in Recurrent/Metastatic Endometrial Cancer: A Study of the Princess Margaret, Chicago, and California Consortia (NCI9322/PHL86)

Clin Cancer Res. 2020 Jun 1;26(11):2477-2486. doi: 10.1158/1078-0432.CCR-19-2576. Epub 2020 Jan 28.


Purpose: The relevance of the MET/hepatocyte growth factor pathway in endometrial cancer tumor biology supports the clinical evaluation of cabozantinib in this disease.

Patients and methods: 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.

Results: 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 CTNNB1 mutation [four partial responses (PRs) in 10 patients, median PFS 7.6 months] and concurrent KRAS and PTEN/PIK3CA mutations (three PRs in 12 patients, median PFS 5.9 months).

Conclusions: Cabozantinib has activity in serous and endometrioid histology endometrial cancer. These results support further evaluation in genomically characterized patient cohorts.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anilides / therapeutic use*
  • California
  • Carcinosarcoma / drug therapy*
  • Carcinosarcoma / secondary
  • Cohort Studies
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Pyridines / therapeutic use*
  • Survival Rate


  • Anilides
  • Pyridines
  • cabozantinib

Associated data