Phase II evaluation of copanlisib, a selective inhibitor of PI3KCA, in patients with persistent or recurrent endometrial carcinoma harboring PIK3CA hotspot mutations: An NRG Oncology study (NRG-GY008) Journal Article
| Authors: | Santin, A. D.; Filiaci, V.; Bellone, S.; O'Cearbhaill, R.; Ratner, E. S.; Mathews, C. A.; Cantuaria, G.; Gunderson, C. C.; Rutledge, T.; Buttin, B. M.; Lankes, H. A.; Birrer, M. J. |
| Article Title: | Phase II evaluation of copanlisib, a selective inhibitor of PI3KCA, in patients with persistent or recurrent endometrial carcinoma harboring PIK3CA hotspot mutations: An NRG Oncology study (NRG-GY008) |
| Abstract: | Purpose: NRG Oncology conducted a phase II trial to assess the antitumor activity and tolerability of copanlisib, a selective inhibitor of PIK3CA, in persistent or recurrent endometrial carcinoma harboring hotspot PIK3CA mutations. Patients and methods: Eligible patients had endometrial cancer with endometrioid, serous or mixed histology, a somatic PIK3CA gene mutation, measurable disease, and GOG performance status ≤2. Treatment consisted of IV copanlisib (60 mg weekly, day 1, 8 and 15 of 28-day cycle) until disease progression or prohibitive toxicity. The primary endpoints of the study were objective tumor response as assessed by RECIST 1.1 and to determine the nature and degree of toxicity of copanlisib as assessed by CTCAE version 4. The study used a 2-stage group sequential design. Results: Eleven patients were enrolled onto stage I of the treatment trial. Five patients had endometrioid, four serous and two had a tumor of mixed histology. The most common PIK3CA mutation was Q546X (n = 3) in exon 9. The most common grade 3 or 4 AE was hyperglycemia. No grade 5 adverse events were reported. No clinical responses were detected. Six patients had a best overall response of stable disease. Of 11 who initiated treatment, 10 progressed on treatment. One patient with stable disease on copanlisib withdrew from treatment secondary to relocation. The median progression-free survival (PFS) was 2.8 months; at 6 months 27% were alive, progression-free. The median overall survival (OS) was 15.2 months. Due to the lack of CR/PR continuation of accrual to the second stage of accrual was not warranted. Conclusion: Copanlisib is well tolerated but has limited activity as a single agent in this population. © 2020 The Authors |
| Keywords: | adult; cancer survival; clinical article; treatment response; aged; gene mutation; overall survival; exon; cancer recurrence; drug withdrawal; endometrium carcinoma; endometrial neoplasms; progression free survival; infection; multiple cycle treatment; phase 2 clinical trial; kidney disease; phosphatidylinositol 3 kinase; hyperglycemia; drug response; mental disease; recurrent disease; skin disease; connective tissue disease; neurologic disease; gastrointestinal disease; metabolic disorder; disease exacerbation; thorax disease; musculoskeletal disease; hematologic disease; vascular disease; respiratory tract disease; breast disease; pik3ca; urinary tract disease; mediastinum disease; nutritional disorder; human; female; priority journal; article; copanlisib; infestation; targeted treatment |
| Journal Title: | Gynecologic Oncology Reports |
| Volume: | 31 |
| ISSN: | 2352-5789 |
| Publisher: | Elsevier B.V. |
| Date Published: | 2020-02-01 |
| Start Page: | 100532 |
| Language: | English |
| DOI: | 10.1016/j.gore.2019.100532 |
| PROVIDER: | scopus |
| PMCID: | PMC6951478 |
| PUBMED: | 31934607 |
| DOI/URL: | |
| Notes: | Article -- Corrigendum issued, see DOI 10.1016/j.gore.2020.100590 -- Export Date: 15 December 2020 -- Source: Scopus |
