Durvalumab maintains NSCLC patient-reported outcomes

Durvalumab provides clinically meaningful improvements in non–small cell lung cancer (NSCLC) without diminishing patient-reported outcomes (PROs), based on data from the phase 3 PACIFIC trial.

This finding further supports durvalumab (Imfinzi) as a new standard of care for patients with locally advanced, unresectable NSCLC who have received concurrent chemoradiotherapy, according to lead author Rina Hui, MBBS, PhD, of the University of Sydney, and colleagues. Maintaining PROs is essential to a positive patient experience and as a benchmark, since the previous standard of care – observation – also kept PROs stable, they noted.

“Improved survival is an important endpoint, but this endpoint is not the only measure of benefit,” the investigators wrote in Lancet Oncology.

“Although safety endpoints provide evidence for treatment toxicity, they are assessed directly by clinical investigators and they do not provide insight into subjective patient experience. Therefore, PROs, which reflect patients’ perspective of their symptoms, functioning, and health-related quality of life, can provide important complementary data to efficacy and safety endpoints.” The investigators also pointed out that PROs are now a priority of the Food and Drug Administration’s new Oncology Center of Excellence.

Still, in an exploratory post hoc analysis, which required that a first report of clinically relevant deterioration be confirmed by a second, subsequent time point, delays in worsening of disease-specific pain and overall pain favored durvalumab. “Further, delays in worsening were observed for nausea or vomiting, constipation, insomnia, and haemoptysis with durvalumab relative to placebo,” the investigators wrote, going on to suggest that transient changes in symptoms “might have disproportionately affected the durvalumab group.”

Almost none of the PROs had significant between-group differences in terms of clinically relevant improvements, apart from emotional functioning, which again favored durvalumab (odds ratio, 1.72; range, 1.08-2.76). “This finding might be associated with the improved efficacy observed with durvalumab,” the investigators wrote.

Among key symptoms, only dysphagia and alopecia showed clinically meaningful improvements during the first year. These improvements were observed in both groups, likely because of the “resolution of toxicities related to previous concurrent chemoradiotherapy,” according to the investigators.

“In conclusion, our analyses of PROs showed that the addition of up to 12 months of durvalumab treatment did not compromise patients’ symptoms, functioning, or global health status or quality of life during the study period compared with placebo,” the investigators wrote. “These findings complement the previously reported improvements in progression-free survival and overall survival and investigator-reported toxicity profile with durvalumab and provide evidence to support the PACIFIC regimen (durvalumab after concurrent chemoradiotherapy) as a new standard of care in unresectable, stage 3 non–small cell lung cancer.”

Dr. Anota and Dr. Westeel suggested that the study findings were as expected, considering the methodology. “Since immune-related adverse events affect few patients and severe adverse events remain infrequent, it is not surprising that, overall, quality of life was unaffected,” they wrote. “There is, therefore, a need to detail adverse events in the small proportion of patients who report immune-related adverse events, who might show deterioration of HRQOL.”

They proposed several ways to improve accuracy of PROs for future immunotherapy studies, including the use of time to deterioration without confirmation (as was the case in the post hoc analysis), a narrower minimal clinically important difference (5 vs. 10 points), and longer follow-up.

Ultimately, Dr. Anota and Dr. Westeel considered the present method of analysis “adequate” based on current standards, while also suggesting that these standards need to be updated.

“This study highlights the need for more data on HRQOL and new approaches, including new questionnaires items and strategies, to capture clinically meaningful changes in HRQOL in patients receiving immune checkpoint inhibitors.”

The study was funded by AstraZeneca. The investigators reported additional relationships with Novartis, Roche, Bristol-Myers Squibb, and others. Dr. Anota and Dr. Westeel reported financial support from Boehringer Ingelheim, Lilly, Merck Sharp & Dohme, and others.