Durvalumab Delivers on QoL Post Chemo RT in PACIFIC Trial

Patient reported outcomes (PROs) from the PACIFIC trial of durvalumab versus placebo after chemoradiation in locally advanced unresectable non—small cell lung cancer (NSCLC) show that durvalumab had no serious impact on quality of life (QoL), which is important because survival gains should be balanced with an acceptable QoL, investigators said at the IASLC 18th World Conference on Lung Cancer (WCLC).

The phase III, double blind, placebo-controlled PACIFIC trial demonstrated median progression-free survival (PFS) for durvalumab of 16.8 months (95% CI, 13.0-18.1) versus 5.6 months (95% CI, 4.6-7.8) for placebo. The 12-month PFS rate was 55.9% for durvalumab (95% CI, 51.0-60.4) and 35.3% (95% CI, 29.0-41.7), for placebo; and the 18-month PFS rate was 44.2% (95% CI, 37.7-50.5) and 27% (95% CI, 19.9-34.5), respectively.

PRO information was gathered at regular intervals starting with the baseline at about 6 weeks post chemoradiation therapy, continuing until day 30 following discontinuation. Investigators noted high levels of compliance with PRO questionnaire tools: >80% through week 48. The patient allotment was roughly 2:1 durvalumab (n = 476) versus placebo (n = 237).

Investigators measured symptoms, physical function, and global health status/QoL using the EORTC QLQ-C30 v3 questionnaire and its lung cancer module QLQ-LC13. The surveys were administered at baseline, week 4, and week 8; then, every 8 weeks until week 48, and then every 12 weeks until disease progression. Odds of improvement and time to deterioration were analyzed.

At baseline, scores were low and evenly matched between the durvalumab and placebo arms for such symptoms as coughing, dyspnea, chest pain, fatigue, and appetite loss, meaning that most patients did not report undue discomfort from these issues. Those same key symptoms remained stable throughout the study for both durvalumab and placebo, and no significant differences were seen between arms in changes from baseline for key symptoms.

Similarly, scores were high and evenly matched across the arms for physical function and global health status/QoL, indicating relative patient well-being, investigators said. “Functioning and global health status scores remained stable throughout the study with no significant differences between arms in changes from baseline,” said lead presenter Rina Hui, MBBS, FRACP, PhD, senior staff specialist, Crown Princess Mary Cancer Center in Sydney, Australia.

Investigators also noted clinically meaningful improvements in each arm, from baseline, by week 48 for dysphagia and alopecia. The mean dysphagia score at baseline was 21.5 for durvalumab, improving to 6.5 at week 48. For alopecia, the respective durvalumab scores were 26.5 versus 2.7. In the placebo arm, the mean dysphagia baseline score was 23.1 versus 4.1 at week 48. The respective numbers for alopecia were 25.4 and 2.8.

Calculating odds of improvement in function and symptoms, investigators found that improvement in appetite loss was greater with durvalumab versus placebo (OR 1.72; 95% CI, 1.04-2.85). They found that “other pain,” as distinguished from chest, arm, and shoulder pain, took longer to deteriorate with durvalumab compared with placebo (HR 0.72; 95% CI, 0.58-0.89).

“Besides appetite loss and other pain, there were no differences in odds of improvement or time to deterioration,” Hui said. “It is pleasing to see that adding durvalumab for 12 months after chemoradiation therapy did not compromise QoL. Alongside the positive efficacy and safety data for PACIFIC, these PRO findings further support the clinical value of durvalumab in this earlier-stage disease setting.”

PRO information such as this helps oncologists to understand a different aspect of how treatments work, said Michael Boyer, MBBS, FRACP, PhD, chief clinical officer and conjoint chair of Medical Oncology at the Chris O’Brien Lifehouse cancer treatment center in Camperdown, Australia. He presented an analysis of the findings Hui delivered at WCLC. “It’s very relevant that the primary outcome of [PACIFIC] for the first time in a very long time shows a significant improvement in outcome for our patients, in terms of PFS with a hazard ratio of about .5 and about a 20% improvement in PFS at 12 and 18 months,” he said. But the primary outcome must be understood in the context of “how our treatments work,” he said. “Do they have a good effect on symptoms, and in a randomized setting, are there differences between treatments?”

Physicians can make these assessments using their own perception or formalized ratings systems, “but there’s an abundance of evidence that shows we get it wrong very often, and the patients’ own perceptions are what matters here,” Boyer said. The fundamental reason for the PRO gathering discussed by Hui was “to ensure that the gains that could be achieved by an improvement in survival are not offset by a negative impact on quality of life.”

Boyer offered praise for the quality of PRO tools used in the study but also noted limitations. “The amount of data we have as the trial goes on gets less and less.” Further, randomization occurred about 6 weeks following the conclusion of chemotherapy radiation treatment, and patients’ QoL may well have changed in just that interval. “It means that we can’t gauge the entire experience of patients from the time of diagnosis,” Boyer said.

In addition, data were collected only up to the time of progression, meaning that the amount of data amassed from the separate arms is going to differ. “It is highly likely that there were less data coming from the control arm as more patients progressed. If there is a bias associated with it, it will make the control arm look better.” Furthermore, progressing patients, who are excluded from the study, are liable to have worse QoL.

However, analysis of data from studies of patients on pembrolizumab and nivolumab treated over the long term also show that treatment with immune inhibitors results in a “fairly static quality of life. There’s not a lot of deterioration. That’s [also] what we observed with durvalumab,” Boyer said.

Results from the PACIFIC study demonstrated that durvalumab improved PFS, and although there is a need to wait for overall survival results, the improvement occurred without an associated deleterious effect on QoL. “[Because] there was no meaningful differences between the arms, I think this represents an important advance in the treatment of unresectable NSCLC,” he concluded.

Hui R, Ozguroğlu M, Daniel D, et al. Patient-reported outcomes with durvalumab after chemoradiation in locally advanced unresectable NSCLC: data from PACIFIC. Presented at: IASLC 18th World Conference on Lung Cancer; October 15-18, 2017; Yokohama, Japan. Abstract PL 02.02.