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Buparlisib Shows Promise in Metastatic Breast Cancer | Breast Cancer Arabia
  • Buparlisib Shows Promise in Metastatic Breast Cancer

    Buparlisib Shows Promise in Metastatic Breast Cancer

    NEW YORK (Reuters Health) – Buparlisib combined with letrozole shows promise in treating estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer, according to the early-phase Stand Up to Cancer study.
     

    “The combination of letrozole and buparlisib was overall safe and well tolerated, and clinical activity was seen regardless of the presence of a PIK3CA mutation in the tumor,” lead author Dr. Ingrid A. Mayer from Vanderbilt University in Nashville, Tennessee, told Reuters Health by email.
     

    “Results from the ongoing phase III trials are eagerly awaited!” added Dr. Mayer, who is also a consultant to Novartis Pharmaceuticals, which funded the study.
     

    Buparlisib is a reversible pan-PI3K inhibitor that showed a favorable pharmacokinetic profile, with clear evidence of target inhibition and preliminary antitumor activity, in a phase I study.
     

    Dr. Mayer and colleagues investigated the safety and tolerability of oral letrozole, an aromatase inhibitor, in combination with buparlisib in a phase Ib trial of 51 patients with ER-positive metastatic breast cancer refractory to endocrine therapies.
     

    From the beginning dose of 100 mg/d, buparlisib had to be reduced in six patients in the continuous group (the first 20 patients) and in five patients in the intermittent group (the remaining patients), the researchers report in the Journal of Clinical Oncology, online March 24. But fewer than 25% of patients in either group required buparlisib interruption or dose reduction during the first eight weeks of treatment.
     

    The combination of buparlisib and letrozole was well tolerated, with grade 3 adverse events in 14 patients and no grade 4 adverse events, the team found.
     

    Nearly half the patients (45%) experienced mood alterations, but they resolved within two weeks of buparlisib interruption or with administration of selective serotonin reuptake inhibitors. Only one patient permanently discontinued buparlisib because of mood alterations.
     

    Two of 20 patients in the continuous arm achieved a complete and a partial remission, and 11 patients (55%) had stable disease (lasting at least six months in six patients, or 30%).
     

    Although none of the patients in the intermittent arm showed a response, 14 (45%) had stable disease (lasting at least six months in 10 patients, or 32%).
     

    Nine of 20 patients tested had decreased tumor uptake of 18F-FDG 15 days after treatment initiation, and two of these patients had tumor shrinkage on radiographic assessment after two months on treatment.
     

    Dr. Mayer said the eventual role of buparlisib in treatment of breast cancer “will depend on the results of the phase III trial. If the trial achieves its primary endpoint, this will add another important treatment option for patients with ER+ metastatic breast cancer.”
     

    Dr. Jordi Rodon from Vall d’Hebron University Hospital in Barcelona, Spain, has studied buparlisib in advanced solid tumors.
     

    “The idea of the study builds upon the great results from clinical trial Bolero2, where breast cancer patients were treated with anti-hormone therapy plus an mTOR inhibitor,” he told Reuters Health by email. “It is (thought) that buparlisib, being a PI3K inhibitor targeting the same pathway but upstream, may be more efficacious.”
     

    “The idea is to use this study as a first step towards another study for patients recently diagnosed with breast cancer (neoadjuvant setting),” said Dr. Rodon, who was not involved in the new work. “That study is being designed as we speak based on these results.”
     

    Dr. Sara Hurvitz from University of California, Los Angeles, who has studied buparlisib but was not involved in the new research, said the findings are consistent with previous work.
     

    “While the response rate and clinical benefit rate seen with this combination are interesting in a relatively heavily pretreated patient population, these results are similar to (those) seen with other combinations targeting this pathway (such as studies of everolimus-based therapy),” she told Reuters Health by email.
     

    “Randomized studies will need to validate its activity and will need to demonstrate safety relative to other available treatment options in order for it to be utilized in clinical practice,” Dr. Hurvitz said. “The adverse mood effects are a unique and important side effect of this medication that require close medical management and patient education. The fact that it crosses the blood brain barrier is intriguing, though. Hopefully it will turn out to have some activity in brain metastases.”
     

    J Clin Oncol 2014.

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