The clinical efficacy of PD-L1-targeting agent durvalumab as consolidation therapy following standard chemoradiation in patients with unresectable, stage III non-small cell lung cancer (NSCLC) was viewed as ‘potentially practice-changing’ by oncologists in mid-2017.1,2 However, it remains unknown whether these clinical benefits can be translated into symptoms improvement as perceived by patients. Recently, new data presented at the International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer (WCLC) showed that quality of life (QoL) was maintained with survival gains,3 which further supports the clinical value of durvalumab in unresectable NSCLC.
In the PACIFIC trial, durvalumab improved progression-free survival (PFS) by 11.2 months compared with placebo in patients with locally advanced, unresectable stage III NSCLC whose disease did not progress following standard treatment with chemoradiotherapy (16.8 months with durvalumab vs. 5.6 months with placebo; HR=0.52; 95% CI: 0.42-0.65; p<0.001).1,2 This result was greeted with great enthusiasm when the data was first presented at the European Society for Medical Oncology (ESMO) 2017 Congress, as it shows for the first time that immune checkpoint inhibitor is effective outside of the metastatic setting; and more importantly, these outcomes may prompt consideration of this intervention as a new standard of care among this population whose prognosis remains grim (5-year survival rate is only 15%).4
While the clinical efficacy and safety of durvalumab have been reported previously, Dr. Rina Hui of the University of Sydney and Westmead Hospital in Australia recognized the need to study treatment outcome from patient’s perspectives. “[It is important] 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,” she said.5 Notably, patient-reported outcomes from the PACIFIC trial were collected at regular intervals starting with the baseline at about 6 weeks post chemoradiation therapy, continuing until day 30 following discontinuation.5
Dr. Hui reported that patient’s physical function and global health status was maintained throughout the study with no significant differences between arms in changes from baseline.3 While there was generally no change for most symptoms, greater improvements in appetite loss (OR=1.72; 95% CI: 1.04-2.85) and other pain, as distinguished from chest, arm, and shoulder pain (HR=0.72; 95% CI: 0.58-0.89) were noted in durvalumab-treated patients.5
Prof. Michael Boyer, clinical professor of medicine at the University of Sydney, Australia, praised the work of Dr. Hui. While the results of the PACIFIC trial represent “an important advance in the management of unresectable stage III NSCLC”,4 the primary outcome must be understood in the context of “how our treatments work,” Prof. Boyer further explained. “Do they have a good effect on symptoms, and in a randomized setting, are there differences between treatments? There’s an abundance of evidence that shows we get it wrong very often [from a physicians’ perspectives], and the patients’ own perceptions are what matters here,” he said.5
Although durvalumab is not yet approved for use in lung cancer, this study has undoubtedly offers hope for a new therapeutic option that is tolerable with significant health benefits. Prof. Boyer may say this at best, ”researchers contemplating new trials must have felt as if they were banging their heads against a brick wall… Now, a few bricks have fallen away, and blue skies are visible beyond.”4
1. ESMO 2017 Press Release: Durvalumab Improves Progression-free Survival in Stage III Lung Cancer. European Society for Medical Oncology (ESMO). 2017. (Accessed November 6, 2017, at http://www.esmo.org/Conferences/ESMO-2017-Congress/Press-Media/Press-Releases/Durvalumab-Improves-Progression-free-Survival-in-Stage-III-Lung-Cancer.)
2. Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017 [Epub ahead of print].
3. PACIFIC Study Shows Quality of Life is Maintained in Non Small Cell Lung Cancer Patients Treated with Durvalumab after Concurrent Chemoradiation. International Association for the Study of Lung Cancer (IASLC), 2017. (Accessed November 6, 2017, at http://wclc2017.iaslc.org/wp-content/uploads/2017/10/Abstract-10762-Press-Release-Final.pdf.)
4. Durvalumab in Stage III Lung Cancer: ‘An Important Advance’. Medscape, 2017. (Accessed November 6, 2017, at https://www.medscape.com/viewarticle/887160_print.)
5. Durvalumab Delivers on QoL Post Chemo RT in PACIFIC Trial. Onclive, 2017. (Accessed November 6, 2017, at http://www.onclive.com/conference-coverage/wclc-2017/durvalumab-delivers-on-qol-post-chemo-rt-inpacific-trial?p=2.)