A combination of buparlisib and paclitaxel may serve as an effective second-line therapy for patients with recurrent or metastatic squamous cell carcinoma of the head and neck, according to findings from a phase 2 trial.
“Most patients with this type of cancer present with locally advanced disease, which might recur locally or as distant metastatic disease after treatment,” Denis Soulieres, MD, a professor at the department of medicine of Centre Hospitalier de l’Universite de Montreal, and colleagues wrote. “Platinum-based chemotherapy is the standard first-line treatment option, with paclitaxel as a second-line option for platinum-pretreated metastatic disease. However, the unsatisfactory prognosis of patients pretreated with platinum has prompted investigation of novel treatments with targeted agents or immunotherapy.”
Researchers performed a multi-center, randomized, double blind placebo-controlled study of adults with previously treated recurrent or metastatic HNSCC (n = 158) from 58 treatment centers in 18 countries between Nov. 5, 2013, and May 5, 2015. Physicians randomly assigned patients to receive second-line oral buparlisib (100 mg once per day) plus intravenous paclitaxel or placebo plus paclitaxel (80 mg/m2 on days 1, 8, 15 and 22) in treatment cycles of 28 days.
Median PFS was 4.6 months for the buparlisib group (95% CI, 3.5-5.3) and 3.5 months (95% CI, 2.2-3.7) in the placebo group (HR = 0.65; 95% CI, 0.45-0.95). Sixty-two patients (82%) in the buparlisib group experienced grade 3 or grade 4 adverse events, compared with 56 (72%) in the placebo group.
The most common grade 3 or grade 4 adverse events were hyperglycemia (buparlisib, 22% vs. placebo, 3%), anemia (18% vs. 12%) neutropenia (17% vs. 5%) and fatigue (8% vs. 10%).
Overall, 57% of the buparlisib group and 47% of the placebo group experienced serious adverse events. Death occurred in 20% of the buparlisib group and 22% of the placebo group; none were considered treatment-related. Disease progression caused most of the deaths.
“Further phase 3 studies are warranted to confirm this phase 2 finding,” the researchers wrote.
The study did not include patients with active major depression or other mood disorders, Francis P. Worden, MD, an associate professor of the University of Michigan Comprehensive Cancer Center, wrote in an accompanying editorial. Other studies, Worden noted, demonstrated high rates of depression and suicide risk for patients with advanced HNSCC.
“Thus, investigators must remain mindful in their selection of patients for treatment with PI3K inhibitors,” Worden wrote.
“Although buparlisib is far from the cure for recurrent or metastatic squamous cell carcinoma of the head and neck, this drug shows notable activity, beyond what we have yet been able to achieve with cytotoxic chemotherapy in the setting of platinum therapy failures in these patients. As research continues in pursuit of an all-round cure, investigators must continue to capitalize on the genetic changes driving tumorigenesis, using specific targets to tailor treatments.” – by Andy Polhamus
Disclosure: Worden reports advisory roles with Bristol-Myers Squibb, Genzyme and Merck, as well as funding from AstraZeneca, Bristol-Myers Squibb and Merck, all outside of the submitted work. Solieres reports grants or honoraria from Novartis during the study.