Practice Update: ESMO 2018 - Alpelisib Plus Fulvestrant for Hormone Receptor Positive Metastatic Breast Cancer

Director of Saint Luke's Hospital of Kansas City's Koontz Center for Advanced Breast Cancer, Timothy Pluard, M.D., talks with Practice Update about the SOLAR1 trial results presented at ESMO18 and shares why this is important news for patients with HR-positive advanced breast cancer who have the P13K mutation.

Watch Dr. Pluard's interview here, at Practice Update: ESMO 2018: Alpelisib Plus Fulvestrant for Hormone Receptor Positive Metastatic Breast Cancer.

Dr. McGregor: So obviously, there’s been several exciting trials presented at ESMO regarding the treatment and management of breast cancer and one of them is the SOLAR-1 trial. So, can you remind us what question is being asked in this trial?

Dr. Pluard: Well, just as a way of background. We know that PI3-kinase mutations are the most common mutations in hormone receptor positive breast cancer and we’ve been trying to develop a PI3-kinase inhibitor that could effectively address that mutation. And it’s been a challenge because of the off target toxicity to find one that was effective and yet tolerable by the patients. So, this trial looks at alpelisib, a PI3-kinase alpha-specific inhibitor, in combination with fulvestrant in the second line therapy for patients with advanced hormone receptor-positive disease. And so, patients were randomized to alpelisib or a placebo along with fulvestrant, and it showed a significant improvement in those patients who had PI3-kinase mutations for the alpelisib arm.

Dr. McGregor: And how common is this PI3-kinase mutation?

Dr. Pluard: So, about 40% of patients with advanced breast cancer will harbor mutations in PI3-kinase. So it’s a significant population that could be impacted by this.

Dr. McGregor: And so, you mentioned prior studies have been limited by toxicities. Have there been other studies exploring PI3-kinase in this patient population and have we seen similar results in the past?

Dr. Pluard: We have not seen such effective results in part because of the inability for patients to tolerate the drug and stay on trial. So there are off targets of hyperglycemia and rash, which have been limiting in the past, but with this particular agent were quite manageable.

Dr. McGregor: So you pointed out there was a benefit in those who harbor that mutation. So what were the actual findings from the trial?

Dr. Pluard: So, in the control group with the PI3-kinase mutation, the PFS was just over 5 months, and in the treated arm with the alpelisib, it was 11 months. It has a ratio of about 0.65 and it’s a proof of principle that it’s targeting the actual mutation. There was a group of patients who were PI3-kinase wild type and they showed no benefit.

Dr. McGregor: As a result of this study, how is this going to change management for your patients? Is this going to become a standard that patients with breast cancers have a PI3-kinase mutation analysis?

Dr. Pluard: Well, interestingly, you know the majority of patients right now with hormone receptor-positive disease are getting a CDK4/6 inhibitor first line. So, this second-line trial had a small percentage of patients, about 6%, who had prior CDK4/6 inhibitor. Small, obviously, group of patients but they seemed to benefit just as much as those who had not had prior CDK4/6 inhibitors. So I think that this, once it's approved, will be an option for patients who have progressed on previous endocrine therapy with or without CDK4/6 inhibitor, and just adds another tool in the treatment of hormone receptor-positive disease.