Health-Related Quality of Life Outcomes in Patients with Resected Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer Who Received Adjuvant Osimertinib in the Phase III ADAURA Trial

Margarita Majem, Jonathan W Goldman, Thomas John, Christian Grohe, Konstantin Laktionov, Sang-We Kim, Terufumi Kato, Huu Vinh Vu, Shun Lu, Shanqing Li, Kye Young Lee, Charuwan Akewanlop, Chong-Jen Yu, Filippo de Marinis, Laura Bonanno, Manuel Domine, Frances A Shepherd, Shinji Atagi, Lingmin Zeng, Dakshayini Kulkarni, Nenad Medic, Masahiro Tsuboi, Roy S Herbst, Yi-Long Wu, Margarita Majem, Jonathan W Goldman, Thomas John, Christian Grohe, Konstantin Laktionov, Sang-We Kim, Terufumi Kato, Huu Vinh Vu, Shun Lu, Shanqing Li, Kye Young Lee, Charuwan Akewanlop, Chong-Jen Yu, Filippo de Marinis, Laura Bonanno, Manuel Domine, Frances A Shepherd, Shinji Atagi, Lingmin Zeng, Dakshayini Kulkarni, Nenad Medic, Masahiro Tsuboi, Roy S Herbst, Yi-Long Wu

Abstract

Purpose: In the phase III ADAURA trial, adjuvant treatment with osimertinib versus placebo, with/without prior adjuvant chemotherapy, resulted in a statistically significant and clinically meaningful disease-free survival benefit in completely resected stage IB-IIIA EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC). We report health-related quality of life (HRQoL) outcomes from ADAURA.

Patients and methods: Patients randomized 1:1 received oral osimertinib 80 mg or placebo for 3 years or until recurrence/discontinuation. HRQoL (secondary endpoint) was measured using the Short Form-36 (SF-36) health survey at baseline, 12, and 24 weeks, then every 24 weeks until recurrence or treatment completion/discontinuation. Exploratory analyses of SF-36 score changes from baseline until week 96 and time to deterioration (TTD) were performed in the overall population (stage IB-IIIA; N = 682). Clinically meaningful changes were defined using the SF-36 manual.

Results: Baseline physical/mental component summary (PCS/MCS) scores were comparable between osimertinib and placebo (range, 46-47) and maintained to Week 96, with no clinically meaningful differences between arms; difference in adjusted least squares (LS) mean [95% confidence intervals (CI), -1.18 (-2.02 to -0.34) and -1.34 (-2.40 to -0.28), for PCS and MCS, respectively. There were no differences between arms for TTD of PCS and MCS; HR, 1.17 (95% CI, 0.82-1.67) and HR, 0.98 (95% CI, 0.70-1.39), respectively.

Conclusions: HRQoL was maintained with adjuvant osimertinib in patients with stage IB-IIIA EGFRm NSCLC, who were disease-free after complete resection, with no clinically meaningful differences versus placebo, further supporting adjuvant osimertinib as a new treatment in this setting. See related commentary by Patil and Bunn, p. 2204.

Trial registration: ClinicalTrials.gov NCT02511106.

©2022 The Authors; Published by the American Association for Cancer Research.

Figures

Figure 1.
Figure 1.
Compliance rates with the SF-36 survey in the overall population. Compliance rates were calculated as the number of evaluable forms (n) divided by the number of expected forms (N), multiplied by 100, at 12- or 24-week intervals from baseline to week 156. The expected number of SF-36 forms is shown under each timepoint. SF-36, Short Form-36 health survey.
Figure 2.
Figure 2.
Baseline T-scores of the SF-36 component summaries and health domains in the overall population. The red dashed line shows the mean 2009 U.S. population SF-36 normative mean calculated from a sample of adults aged ≥18 years, including healthy individuals, and those with chronic conditions (31); normative data are not age-adjusted. The gray dashed lines show this normative mean ± 1SD. The number of patients with data available at each visit is shown below each component summary and health domain. MCS, mental component summary; PCS, physical component summary; SF-36, Short Form-36 health survey.
Figure 3.
Figure 3.
Change in SF-36 (A) PCS and (B) MCS T-scores from baseline to week 96 in the overall population. The data shown are mean change from baseline in T-scores with error bars representing the SDs. The number of patients with data available at each visit is shown below each timepoint. MCS, mental component summary; PCS, physical component summary; SF-36, Short Form-36 health survey.
Figure 4.
Figure 4.
TTD of the SF-36 (A) PCS and (B) MCS in the overall population. Kaplan–Meier plots are shown for the TTD analysis using clinically meaningful differences defined in the 3rd edition of the SF-36 scoring manual (31). The number of TTD events in MCS/PCS or death (n) in the overall population (N) are shown along with the HRs and 95% CIs comparing the treatment arms. The analysis was performed using an unstratified log-rank test due to low event counts. Crosses indicate censored patients, and the number of patients at risk is shown below each timepoint. CI, confidence interval; MCS, mental component summary; PCS, physical component summary; SF-36, Short Form-36 health survey; TTD, time to deterioration.
Figure 5.
Figure 5.
Forest plot of the TTD of the SF-36 health domains in the overall population. The TTD analysis used clinically meaningful differences defined in the 3rd edition of the SF-36 scoring manual (31) and was performed using an unstratified log-rank test due to low event counts. HRs and corresponding 95% CIs are shown for each health domain along with the number of events (n) in the overall population (N). An HR <1 favors osimertinib treatment. CI, confidence interval; SF-36, Short Form-36 health survey; TTD, time to deterioration.

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