A randomized phase 2 study of sapanisertib in combination with paclitaxel versus paclitaxel alone in women with advanced, recurrent, or persistent endometrial cancer Journal Article
| Authors: | Han, S. N.; Oza, A.; Colombo, N.; Oaknin, A.; Raspagliesi, F.; Wenham, R. M.; Braicu, E. I.; Jewell, A.; Makker, V.; Krell, J.; Alía, E. M. G.; Baurain, J. F.; Su, Z.; Neuwirth, R.; Vincent, S.; Sedarati, F.; Faller, D. V.; Scambia, G. |
| Article Title: | A randomized phase 2 study of sapanisertib in combination with paclitaxel versus paclitaxel alone in women with advanced, recurrent, or persistent endometrial cancer |
| Abstract: | Objective: This phase 2 study investigated sapanisertib (selective dual inhibitor of mTORC1/2) alone, or in combination with paclitaxel or TAK-117 (a selective small molecule inhibitor of PI3K), versus paclitaxel alone in advanced, recurrent, or persistent endometrial cancer. Methods: Patients with histologic diagnosis of endometrial cancer (1–2 prior regimens) were randomized to 28-day cycles on four treatment arms: 1) weekly paclitaxel 80 mg/m2 (days 1, 8, and 15); 2) weekly paclitaxel 80 mg/m2 + oral sapanisertib 4 mg on days 2–4, 9–11, 16–18, and 23–25; 3) weekly sapanisertib 30 mg, or 4) sapanisertib 4 mg + TAK-117 200 mg on days 1–3, 8–10, 15–17, and 22–24. Results: Of 241 patients randomized, 234 received treatment (paclitaxel, n = 87 [3 ongoing]; paclitaxel+sapanisertib, n = 86 [3 ongoing]; sapanisertib, n = 41; sapanisertib+TAK-117, n = 20). The sapanisertib and sapanisertib+TAK-117 arms were closed to enrollment after futility analyses. After a median follow-up of 14.4 (paclitaxel) versus 17.2 (paclitaxel+sapanisertib) months, median progression-free survival (PFS; primary endpoint) was 3.7 versus 5.6 months (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.58–1.15; p = 0.139); in patients with endometrioid histology (n = 116), median PFS was 3.3 versus 5.7 months (HR 0.66; 95% CI 0.43–1.03). Grade ≥ 3 treatment-emergent adverse event rates were 54.0% with paclitaxel versus 89.5% paclitaxel+sapanisertib. Conclusions: Our findings support inclusion of chemotherapy combinations with investigational agents for advanced or metastatic disease. The primary endpoint was not met and toxicity was manageable. Trial registration: ClinicalTrials.gov number, NCT02725268 © 2023 The Authors |
| Keywords: | adult; controlled study; human tissue; major clinical study; constipation; fatigue; histopathology; neutropenia; cancer recurrence; doxorubicin; advanced cancer; cancer combination chemotherapy; diarrhea; drug efficacy; drug safety; hypophosphatemia; monotherapy; side effect; gemcitabine; paclitaxel; cancer patient; follow up; endometrial cancer; endometrium cancer; carboplatin; progression free survival; phase 2 clinical trial; anemia; leukopenia; nausea; randomized controlled trial; stomatitis; vomiting; dehydration; peripheral neuropathy; creatinine; creatinine blood level; phosphatidylinositol 3 kinase; abdominal pain; arthralgia; asthenia; coughing; dyspnea; fever; hyperglycemia; hypomagnesemia; confidence interval; alanine aminotransferase; aspartate aminotransferase; multicenter study; urinary tract infection; peripheral edema; open study; hazard ratio; alopecia; metastatic; advanced; recurrent; deterioration; decreased appetite; mammalian target of rapamycin complex 1; mammalian target of rapamycin complex 2; upper abdominal pain; human; female; article; sapanisertib; mammalian target of rapamycin complexes 1 and 2 inhibitor; serabelisib |
| Journal Title: | Gynecologic Oncology |
| Volume: | 178 |
| ISSN: | 0090-8258 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2023-11-01 |
| Start Page: | 110 |
| End Page: | 118 |
| Language: | English |
| DOI: | 10.1016/j.ygyno.2023.09.013 |
| PUBMED: | 37839313 |
| PROVIDER: | scopus |
| PMCID: | PMC11100409 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
