The addition of the oral AKT inhibitor Truqap (capivasertib) to Zytiga (abiraterone acetate), prednisone and androgen deprivation remedy (ADT) prolonged investigator-assessed radiographic progression-free survival (rPFS) by 7.5 months in contrast with Zytiga, prednisone, ADT, and placebo in sufferers with PTEN-deficient de novo metastatic hormone-sensitive prostate most cancers, in keeping with outcomes introduced on the 2025 European Society for Medical Oncology Congress.
After a median follow-up of 18.4 months, median rPFS with Truqap was 33.2 months in contrast with 25.7 months for placebo. Median total survival was not but reached on the time of study for both arm. There had been 267 occasions on the time of evaluation, with 129 within the Truqap arm and 138 within the placebo group.
“The first finish level was met, displaying an rPFS profit with Truqap and Zytiga, with constant advantages throughout medical finish factors,” mentioned Dr. Karim Fizazi, medical oncologist at Institut Gustave Roussy and Centre Oscar Lambret. “The rPFS within the management arm was solely 25.7 months, highlighting the poor prognosis of this PTEN inhabitants.”
Within the examine, 1,012 sufferers obtained Zytiga at 1,000 milligrams (mg) with prednisone at 5 mg every day plus ADT. Sufferers had been randomly assigned to Truqap at 400 mg twice every day for 4 days on and three days off (507 sufferers) or matched placebo (505 sufferers). PTEN deficiency was outlined as greater than 90% of malignant cells displaying no cytoplasmic staining by immunohistochemistry. About 25% of screened sufferers met this criterion.
Baseline traits had been related between teams. Median age was 67 years with Truqap and 68 years with placebo. Complete Gleason rating was 8 or extra in 78.5% and 79% of sufferers, and illness danger was excessive in 61.3% and 65.9%, respectively. Bone was the first metastatic website in 91.1% and 92.5% of sufferers, and practically two-thirds had an Jap Cooperative Oncology Group efficiency rating of 0, with the rest scoring 1. About three-fourths of sufferers had high-volume illness.
Glossary
Radiographic Development-Free Survival (rPFS): the size of time throughout and after therapy during which a affected person’s most cancers doesn’t worsen as seen on imaging scans, similar to CT, MRI, or bone scans.
Total Survival (OS): the size of time from the beginning of therapy that sufferers are nonetheless alive, no matter illness standing.
Symptomatic Skeletal Occasion-Free Survival: the size of time a affected person lives with out experiencing critical bone-related problems brought on by most cancers, similar to fractures, spinal twine compression, or needing radiation or surgical procedure to the bone.
Castration Resistance: the purpose at which prostate most cancers continues to develop or unfold regardless of therapies that decrease testosterone (similar to ADT).
“In step with the poor prognosis of this PTEN-deficient prostate most cancers inhabitants, most sufferers had high-risk, high-volume, excessive Gleason rating illness,” Fizazi mentioned.
Subgroup analyses confirmed related enhancements in rPFS with Truqap, though none met statistical significance. Time to subsequent therapy was 37 months with Truqap in contrast with 28.5 months for placebo. Median symptomatic skeletal event-free survival was 42.5 months versus 37.3 months. Occasions included pathological fracture, spinal twine compression, radiation use, surgical intervention, and demise.
Time to castration resistance was 29.5 months with Truqap in contrast with 22 months for placebo. Median time to PSA development was not calculable at evaluation, with 60 occasions within the Truqap arm in contrast with 82 in placebo. Ache development was too early to measure.
Analyses by PTEN expression confirmed constant rPFS profit throughout all ranges. With PTEN loss in 100% of cells, median rPFS was 34.1 months with Truqap in contrast with 22.1 months for placebo. Truqap additionally confirmed developments towards improved total survival and secondary finish factors in greater PTEN-deficient populations.
Uncomfortable side effects had been greater with Truqap. Grade 3 (extreme) or greater (life-threatening) negative effects occurred in 67% of sufferers versus 40.4% for placebo. Severe negative effects occurred in 42.5% versus 26%. Uncomfortable side effects led to discontinuation in 18.3% versus 4.8%. Dose interruptions had been required in 62.8% versus 26.8% and dose reductions in 29% versus 3.6%. Uncomfortable side effects resulting in Zytiga discontinuation occurred in 9.5% versus 5.4%.
The most typical negative effects with Truqap in contrast with placebo had been diarrhea (51.9% versus 8%), hyperglycemia (38% versus 12.9%), rash (35.4% versus 7%), anemia (23.9% versus 12.7%), and hypokalemia (22.1% versus 12.7%). “Uncomfortable side effects typical of Zytiga, similar to hypertension, hypokalemia, and elevated liver enzymes, had been related between arms,” Fizazi mentioned.
In early 2025, one other examine exploring Truqap together with docetaxel and ADT was halted after an interim evaluation advised potential lack of efficacy.
Outdoors prostate most cancers, Truqap is FDA-approved with fulvestrant (Faslodex) for sufferers with hormone receptor-positive, HER2-negative domestically superior or metastatic breast most cancers harboring a number of PIK3CA, AKT1, or PTEN alterations after development on no less than one prior endocrine routine or recurrence inside 12 months of adjuvant remedy.
References
- “A part III examine of capivasertib (capi) + abiraterone (abi) vs placebo (pbo) + abi in sufferers (pts) with PTEN poor de novo metastatic hormone-sensitive prostate most cancers (mHSPC): CAPItello-281,” by Dr. Karim Fizazi, et al. Offered at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Summary 2383O.
- Replace on CAPItello-280 part III trial of Truqap in metastatic castration-resistant prostate most cancers. Information launch. AstraZeneca. April 29, 2025. Accessed Oct. 19, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/update-on-capitello-280-phase-iii-trial.html
- FDA approves capivasertib with fulvestrant for breast most cancers. FDA. November 16, 2023. Accessed Could 1, 2025. https://www.fda.gov/medication/resources-information-approved-drugs/fda-approves-capivasertib-fulvestrant-breast-cancer
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