Copanlisib in Patients With PIK3CA-Mutated Tumors

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In a phase II trial reported in the Journal of Clinical Oncology, Damodaran et al found that the phosphoinositide 3-kinase (PI3K) inhibitor copanlisib exhibited activity in patients who have tumors with PIK3CA mutations.

The study is a subprotocol (Z1F) of the NCI-MATCH ECOG-ACRIN trial (EAY131), a tumor-agnostic platform trial that enrolls patients to receive targeted therapies on the basis of matching genomic alterations.

Study Details

In the trial, 25 response-evaluable patients received copanlisib at 60 mg on days 1, 8, and 15 in 28-day cycles until disease progression or toxicity. Patients with coexisting PTEN loss were permitted; those with KRAS mutations, HER2-positive breast cancer, and lymphoma were excluded. The most common cancers were gynecologic (n = 6) and gastrointestinal (n = 6) malignancies. Most patients had received three or more prior lines of therapy.

The primary endpoint was centrally assessed objective response rate; a response rate of ≥ 16% (vs a null response rate of 5%) permitted the conclusion that the agent exhibited promising activity and was worthy of further investigation.



  • Objective response was observed in 16% of patients.
  • The clinical benefit rate was 36%.

Objective responses (all partial) were observed in four patients (16%, 90% confidence interval [CI] = 6%–33%; P = .0341 vs null rate of 5%). An additional nine patients (36%) had stable disease. Clinical benefit (objective response or stable disease ≥ 6 months) was also observed in nine patients (36%).

Responses were observed in patients with endometrial adenocarcinoma, clear cell carcinoma of the anterior abdominal wall, ameloblastoma of the mandible, and low-grade myxoid liposarcoma. Two patients with response remained on study treatment and had received 28 and 29 cycles of treatment at data cutoff in January 2021.

Median progression-free survival was 3.4 months (90% CI = 1.8–6.6 months), with a 6-month rate of 38% (90% CI = 22%–53%). Median overall survival was 5.9 months (90% CI = 4.9–13.7 months), with a 6-month rate of 50% (90% CI = 32%–65%).  

Adverse Events

Among 30 patients included in the safety population, treatment-related grade 3 adverse events occurred in 53%, with a grade 4 event observed in 1 patient (3%). The most common adverse events were hypertension (30%), hyperglycemia (grade 3 in 23%, grade 4 in 3%), maculopapular rash (7%), generalized muscle weakness (7%), and dehydration (7%). The most common treatment-related adverse events of any grade were hyperglycemia (63%), fatigue (40%), and diarrhea (37%). Adverse events led to treatment discontinuation in three patients (10%).

The investigators concluded, “The study met its primary endpoint with an objective response rate of 16% (P = .0341) with copanlisib showing clinical activity in select tumors with PIK3CA mutation in the refractory setting.”

Senthil Damodaran, MD, PhD, of The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit

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