Taselisib Hits, but Barely Slows, PI3KCA-Mutated Breast Cancer

Nick Mulcahy

June 02, 2018

CHICAGO — The investigational targeted therapy taselisib (Roche) slowed the growth of advanced breast cancer by 2 months when used in combination with fulvestrant (Faslodex, AstraZeneca) compared with the aromatase inhibitor alone in patients who had experienced hormonal resistance to earlier therapies, according to results from the SANDPIPER study.

However, taselisib's "modest" efficacy in terms of progression-free survival (PFS) is accompanied by a "challenging tolerability," said lead investigator José Baselga, MD, from Memorial Sloan Kettering Cancer Center in New York City.

He was speaking a press briefing here at American Society of Clinical Oncology (ASCO) 2018.

Nevertheless, Baselga said that the results were "proof of principle that this is a bona fide target."

Taselisib is the first agent that targets PIK3CA mutations, which are among the most common genetic aberrations in breast cancer and, as such, are an obvious target for drug development, but these new results only inspired muted praise.

"It's is an important step forward because it does suggest that we can effectively target the pathway," said Harold Burstein, MD, an ASCO expert from the Dana Farber Cancer Institute in Boston, Massachusetts, who spoke at the press conference.

Richard Shilsky, MD, the ASCO chief medical officer, who moderated the press conference, observed that other PI3 kinase inhibitors are approved and used in hematologic cancers and that these new results are the first sign of efficacy, albeit "modest," in a solid tumor. He commented to Medscape Medical News that the results were "statistically significant but not clinically gigantic."

Another expert also focused on the conceptual significance of the trial.

The new study "provides important evidence that targeting the PI3K pathway has an impact in advanced breast cancer," said Darcy Spicer, MD, from the University of Southern California Norris Cancer Center in Los Angeles, in comments to Medscape Medical News.

Baselga and co-investigators enrolled 516 postmenopausal women with locally advanced or metastatic estrogen receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer who had disease recurrence or progression during or after an aromatase inhibitor. The women were randomly assigned 2:1 to receive taselisib (n=340; 4 mg oral, once a day) or placebo plus fulvestrant (n=176; 500 mg).

For the primary outcome of PFS, taselisib provided a median PFS of 7.4 months compared with 5.4 months with placebo. This translated into a 30% reduction in the relative risk for progression (hazard ratio, 0.70; P = .0037) with taselisib.

The response rate to treatment was doubled with taselisib (28% vs 11.9%). Overall survival data are not yet available.

But the targeted therapy's benefit came at the cost of greater toxicity, reported Baselga.

The rate of serious adverse effects for taselisib vs placebo was 32% vs 8.9%. For grade 3 or worse adverse effects, the rates were 49.5% vs 16.4%. The targeted therapy also led to more discontinuations (16.8% vs 2.3%).

Gastrointestinal toxicities were the most frequently seen adverse event with taselisib, with diarrhea (all grades) at 60.1% vs 19.7%. Hyperglycemia was also common, at 40.4% vs 9.4%.

Postmenopausal women with this type of metastatic breast cancer who had disease recurrence or progression during or after an aromatase inhibitor have other treatment options, including CDK4/6 inhibitors. Those drugs have demonstrated an improvement in PFS of 8 to 12 months in clinical trials of these same women, pointed out Burstein.

The study was funded by Roche. Baselga has multiple financial ties to industry. Some authors are employees of Roche. Burstein and Shilsky have disclosed no relevant financial relationships.

American Society of Clinical Oncology (ASCO) 2018: Abstract LBA1006. Presented June 4, 2018.

Follow Medscape senior journalist Nick Mulcahy on Twitter: @MulcahyNick

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