Patient-reported outcome data support perioperative durvalumab for operable NSCLC

In patients with resectable nonsmall cell lung cancer (NSCLC), adding perioperative durvalumab to neoadjuvant chemotherapy does not appear to have a detrimental impact on patient-reported health-related quality of life (QoL), functioning, or symptoms as compared with neoadjuvant chemotherapy alone, according to data from the phase III AEGEAN study.

Analysis using a mixed model for repeated measures showed no clinically meaningful changes from baseline in global health status (GHS)/QoL scores in either treatment arm during the neoadjuvant period (average mean change, –2.6 with durvalumab and –1.9 with placebo) and the adjuvant period (average mean change, 1.4 and 4.6, respectively), reported lead researcher Dr Giulia Pasello from the Istituto Oncologico Veneto IRCCS in Padua, Italy. [ELCC 2025, abstract 188O]

The same was true for physical functioning and role functioning, with the average mean change in scores from baseline not exceeding the 10-point threshold of clinically meaningful, Pasello added.

In the durvalumab arm, the average mean physical functioning scores decreased by 4.0 points during the neoadjuvant period and increased by 3.4 points during the adjuvant period, while the average mean role functioning scores decreased by 6.5 points and increased by 3.2 points during the respective periods. Changes seen in the placebo arm were similar (physical functioning scores: –3.1 points during the neoadjuvant period and 3.9 points during the adjuvant period; role functioning scores: –5.1 and 4.8 points during the respective periods).

In terms of patient-reported symptoms, a trend towards improvement in coughing was observed across all timepoints during the neoadjuvant period. Average mean coughing scores dropped by 6.5 points in the durvalumab arm and by 8.2 points in the placebo arm.

Meanwhile, fatigue and appetite loss showed a trend for improvement during the adjuvant period. Average mean fatigue scores declined by 2.7 points in the durvalumab arm and by 5.1 points in the placebo arm, while average mean appetite loss scores decreased by 7.8 and 8.3 points, respectively.

The time to deterioration of physical and role functioning, as well as GHS/QoL, fatigue, and appetite loss did not differ between the durvalumab and placebo arms during the adjuvant period.

Exploratory analyses indicated low patient reported symptom burden, assessed using the Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO CTCAE) questionnaire, in both treatment arms at neoadjuvant baseline, Pasello noted.

“There were no apparent between-arm differences in the proportions of patients reporting treatment related symptoms, except patients reporting rash, which was more prevalent in the durvalumab arm, particularly during neoadjuvant treatment,” she added.

The efficacy and safety of perioperative durvalumab plus neoadjuvant chemotherapy vs neoadjuvant chemotherapy alone have already been shown in the first and second interim analyses of the AEGEAN study. Specifically, the addition of perioperative durvalumab yielded improvements in pathological complete response and event-free survival, with a manageable AE profile and no new safety signals emerging. Pasello pointed out that these data led to global approvals of durvalumab for the perioperative treatment of resectable NSCLC. [J Thorac Oncol 2020;15:709-740; N Engl J Med 2023;389:1672-1684. J Thorac Oncol 2024;19:S38-S39]

“Together with the significant efficacy improvements and manageable safety profile, the patient-reported outcomes (PROs) further support perioperative durvalumab as a new treatment option for patients with resectable NSCLC,” Pasello said.

Data for the PRO analysis were collected using the following: the EORTC Core Quality of Life questionnaire (EORTC QLQ-C30), the EORTC Quality of Life Questionnaire - Lung Cancer Module (EORTC QLQ LC13), and PRO CTCAE. Questionnaire completion rates remained high in both arms across all visits: >79 percent for QLQ C30, >86 percent for QLQ LC13, and >79 percent for PRO CTCAE. A ≥10-point change in PRO scores (range, 0–100) was deemed clinically meaningful.

AEGEAN included patients with treatment-naïve, resectable stage IIA-IIIB NSCLC with plans to undergo lobectomy, sleeve resection, or bilobectomy. The patients had to have an ECOG performance status of 0 or 1, confirmed PD-L1 status, and no documented EGFR or ALK aberrations.

A total of 802 patients were randomly assigned to receive neoadjuvant therapy consisting of 1,500 mg of intravenous (IV) durvalumab plus platinum-based chemotherapy every 3 weeks for 4 cycles (durvalumab arm), or IV placebo plus platinum-based chemotherapy on the same schedule (placebo arm). After surgery, an additional 12 cycles of durvalumab or placebo every 4 weeks were given. Postoperative radiotherapy was allowed in accordance with local guidance. The neoadjuvant period included the modified intention-to-treat population, while the adjuvant period involved the modified resected population.