Taselisib or Placebo With Fulvestrant in ER-Positive, PIK3CA-Mutant

Taselisib or Placebo With Fulvestrant in ER-Positive, PIK3CA-Mutant, HER2-Negative Advanced Breast Cancer

The phase III SANDPIPER study assessed taselisib (GDC-0032), a potent, selective PI3K inhibitor, plus fulvestrant in estrogen receptor-positive, HER2-negative, PIK3CA-mutant locally advanced or metastatic breast cancer.

TAKE-HOME MESSAGE
Patients with estrogen receptor–positive, HER2-negative advanced/metastatic breast cancer treated with fulvestrant were randomized to receive the PIK3CA inhibitor taselisib or placebo. The addition of taselisib to fulvestrant was associated with a significant increase in progression-free survival (7.4 months vs 5.4 months) and objective response rate (28.0% vs 11.9%) compared with placebo. The side-effect profile of taselisib was as expected overall, with the most common side effects being diarrhea, hyperglycemia, nausea, decreased appetite, fatigue, headache, stomatitis, vomiting, asthenia, and rash. There was a significantly higher proportion of grade 3–5 adverse events in the taselisib arm compared with the placebo arm, and adverse events led to more discontinuations and dose interruptions with taselisib versus placebo.

Given the overall toxicity profile and tolerability, the authors conclude that taselisib plus fulvestrant has limited clinical utility despite the modest increase in progression-free survival and objective response seen in this trial.

Conclusion
SANDPIPER met its primary endpoint; however, the combination of taselisib plus fulvestrant has no clinical utility given its safety profile and modest clinical benefit.

Observation
The PIK3CA alpha sub unit–specific inhibitor alpelisib was studied in combination with fulvestrant in a similar clinical population in the SOLAR-1 trial. Alpelisib doubled the median PFS in this study in PI3KCA-mutated patients, with somewhat less toxicity, and is now approved in this setting. All patients with HR+/HER2− MBC should undergo testing for PIK3CA mutations to assess eligibility for this important treatment, preferably at the diagnosis of metastatic disease so comprehensive treatment planning can proceed. Recent data have confirmed the benefit of alpelisib and fulvestrant even after CDK4/6 therapy in the first-line setting, a group underrepresented in the SOLAR-1 registration trial. Further development of potent selective PI3K inhibitors is underway.

Hello Paxalisib, Genentech would now surely be interested in acquiring back their out-licensed drug (with low toxicity) for HER2+ BCBM, after Genentech's disappointing trial above,

https://www.practiceupdate.com/c/109370/67/13/?elsca1=emc_enews_weekinreview&elsca2=email&elsca3=practiceupdate_metastaticbreastcancer&elsca4=metastaticbreastcancer&elsca5=newsletter&rid=NDQ3MTgxOTYwMzc4S0&lid=10332481

Regards.