TY - JOUR
T1 - Phase II evaluation of copanlisib, a selective inhibitor of Pi3kca, in patients with persistent or recurrent endometrial carcinoma harboring PIK3CA hotspot mutations
T2 - An NRG Oncology study (NRG-GY008)
AU - Santin, Alessandro D.
AU - Filiaci, Virginia
AU - Bellone, Stefania
AU - Ratner, Elena S.
AU - Mathews, Cara A.
AU - Cantuaria, Guilherme
AU - Gunderson, Camille C.
AU - Rutledge, Teresa
AU - Buttin, Barbara M.
AU - Lankes, Heather A.
AU - Frumovitz, Michael
AU - Khleif, Samir N.
AU - Huh, Warner K.
AU - Birrer, Michael J.
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/2
Y1 - 2020/2
N2 - 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.
AB - 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.
KW - Copanlisib
KW - Endometrial neoplasms
KW - Pik3ca
KW - Targeted treatment
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U2 - 10.1016/j.gore.2019.100532
DO - 10.1016/j.gore.2019.100532
M3 - Article
C2 - 31934607
AN - SCOPUS:85077645974
SN - 2211-338X
VL - 31
JO - Gynecologic Oncology Reports
JF - Gynecologic Oncology Reports
M1 - 100532
ER -