Clinical Trial Participants May Fare Better Than Medicare Beneficiaries Treated with Zydelig

Patients treated with Zydelig (idelalisib) in the clinical setting, compared with those in clinical trials, experienced less favorable outcomes, according to study results published in JAMA Oncology.

“This example supports (Food and Drug Administration) initiatives to broaden trial eligibility criteria and bridge the gap between clinical studies and the intended treatment population,” the researchers wrote.

Zydelig is approved to treat patients with follicular lymphoma as a monotherapy, and also to treat patients with chronic lymphocytic leukemia (CLL) in combination with Rituxan (ritxumab). However, despite its approval, the agent has been found to induce severe and treatment-limiting side effects.

Therefore, the researchers compared outcomes of clinical trial participants in studies 101-09 (a phase 2, single-group, open-label trial supporting the accelerated approval in relapsed or refractory follicular lymphoma) and 312-0116 (a phase 3, multicenter, randomized, double-blind trial supporting approval the combination regimen for relapsed CLL), with those of Medicare beneficiaries — all aged 65 and older, treated with Zydelig for the same disease. Treatment duration, on-treatment, and overall mortality, and serious and fatal infections were compared between clinical trial participants and Medicare beneficiaries.

Overall, there were 26 trial participants and 305 Medicare beneficiaries with follicular lymphoma, and 89 trial participants and 295 beneficiaries with CLL included in the analysis.

The researchers found that Medicare beneficiaries were older with a higher rate of comorbidities. “These differences may have arisen from trial eligibility criteria, which often exclude comorbidities that could negatively affect tolerability,” the researchers wrote.

Medicare beneficiaries with CLL had a shorter median treatment duration, compared with clinical trial participants (173 days vs 473 days); however, this was not seen among those with follicular lymphoma (114, days vs 160 days, respectively).

Medicare beneficiaries from both disease states demonstrated a higher mortality rate and a significantly higher fatal infection rate per 100 person-years, compared with clinical trial participants.

In addition, a hospitalized infection within six months prior to treatment with Zydelig was associated with a 2.11-fold increased risk for on-treatment fatal infections among Medicare beneficiaries.

Patients treated with Zydelig in a clinical trial setting experienced twice as many dose reductions.

“Our study findings are consistent with an internal FDA review of eligibility criteria for oncology trials, finding most trials had a narrowly defined population of lower-risk patients,” the researchers wrote. “Efficacy and tolerability may be meaningfully different for optimally selected and closely monitored trial participants compared with unrestricted patients in the clinical setting.”

They also noted that, despite a recommendation issued in March 2016 in regard to Pneumocystis jirovecii pneumonia prophylaxis in patients treated with Zydelig, rates of the infection were low after that recommendation among those with follicular lymphoma (25%) and CLL (37%).

“Compliance with (Pneumocystis jirovecii) prophylaxis and close monitoring of absolute neutrophil counts, with appropriate dose interruptions and reductions, may help reduce the rate of serious infections,” the researchers concluded.