Brown JR, et al. - The efficacy and safety of voxtalisib (also known as XL765 or SAR245409), a pan-PI3K/mTOR inhibitor, were investigated in patients with relapsed or refractory lymphoma, or chronic lymphocytic leukaemia/small lymphocytic lymphoma. In patients with follicular lymphoma, voxtalisib 50 mg given orally twice daily showed an acceptable safety profile, with promising efficacy but it was observed to have limited efficacy in patients with mantle cell lymphoma, diffuse large B-cell lymphoma, or chronic lymphocytic leukaemia/small lymphocytic lymphoma.

Methods

• A non-randomised, open-label, phase 2 trial was performed at 30 oncology clinics in the USA, Belgium, Germany, France, the Netherlands, and Australia.
• Researchers enrolled patients aged 18 years or older with Eastern Cooperative Oncology Group (EGOG) performance status score of 2 or lower and relapsed or refractory mantle cell lymphoma, follicular lymphoma, diffuse large B-cell lymphoma, or chronic lymphocytic leukaemia/small lymphocytic lymphoma.
• Patients were administered voxtalisib 50 mg orally twice daily in 28-day continuous dosing cycles until progression or unacceptable toxicity.
• The proportion of patients in each disease-specific cohort who achieved an overall response, defined as a complete response or partial response, was the primary endpoint.
• They analyzed all patients who received more than 4 weeks of treatment and who completed a baseline and at least one post-baseline tumour assessment for efficacy.  
• Analysis of all patients was performed for safety.

Results

• Researchers enrolled 167 patients from Oct 19, 2011 to July 24, 2013; 42 with mantle cell lymphoma, 47 with follicular lymphoma, 42 with diffuse large B-cell lymphoma, and 36 with chronic lymphocytic leukaemia/small lymphocytic lymphoma.
• As per observations, the median number of previous anticancer regimens was three (IQR 2–4) for patients with lymphoma and four (2–5) for patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma.
• They recognized 164 patients as evaluable for efficacy.
• Of these, 30 (18·3%) achieved an overall response (partial, n=22; complete, n=8); 19 (41·3%) of 46 with follicular lymphoma, five (11·9%) of 42 with mantle cell lymphoma, two (4·9%) of 41 with diffuse large B-cell lymphoma, and four (11·4%) of 35 with chronic lymphocytic leukaemia/small lymphocytic lymphoma.
• The safety profile of previous studies of voxtalisib was supported by the findings.
• Adverse events, most frequently noted, were diarrhoea (in 59 [35%] of 167 patients), fatigue (in 53 [32%]), nausea (in 45 [27%]), pyrexia (in 44 [26%,]), cough (in 40 [24%]), and decreased appetite (in 35 [21%]).
• Grade 3 or worse adverse events, reported most frequently, were anaemia (in 20 [12%] of 167 patients), pneumonia (in 14 [8%]), and thrombocytopenia (in 13 [8%]).
• In 97 (58·1%) of 167 patients, serious adverse events were noted.