Patients with EGFR-positive non–small cell lung cancer who received treatment with osimertinib following surgery versus placebo experienced no clinically meaningful differences in health-related quality of life, according to results of a pivotal phase 3 trial.
Patients receiving adjuvant osimertinib (Tagrisso) in the phase 3 ADAURA trial (NCT02511106) for EGFR-positive non–small cell lung cancer (NSCLC) experienced no clinically meaningful differences in health-related quality of life (HRQoL) measures versus placebo, according to an analysis on patient-reported outcomes (PROs) from the pivotal trial.1,2
Results indicated a high rate of compliance with regard to the completion of the Short Form-36 (SF-36) health survey, which remained at 85% or higher across all visits in both the osimertinib arm and the placebo arm. Physical component summary scores (PCS) and mental component summary scores (MCS) T-scores were also comparable between the arms (range, 46-47), and were only slightly below the mean values observed in the general population (0.3-0.4 SD below the normative mean).
Patients in both the osimertinib arm and the placebo arm experienced a slight increase from baseline to week 96 in SF-36 PCS, at 1.13 (95% CI, 0.54-1.72) and 2.31 (95% CI, 1.70-2.91), respectively; this was also true with regard to SF-36 MCS, at 1.34 (95% CI, 0.60-2.08) and 2.68 (95% CI, 1.92-3.44), respectively. No clinically meaningful differences were noted between the investigative and control arms of the study (SF-36 PCS, -1.18; 95% CI, -2.02, -0.34; SF-36 MCS, -1.34; 95% CI, ‑2.40, ‑0.28).
While in the disease-free period, more than 80% of patients did not experience a clinically meaningful deterioration in PCS or MCS. For patients who did experience deterioration, no notable differences in time to deterioration (TTD) of PCS (HR, 1.17; 95% CI, 0.82-1.67) or MCS (HR 0.98; 95%CI, 0.70-1.39) were observed in either arm of the study.
"At baseline, we saw that patients had almost the same mean value QoL as the normal population,” lead study author Margarita Tarruella, MD, PhD, a faculty member in the Department of Medical Oncology at the Hospital de la Santa Creu i Sant Pau, said in an interview leading up to the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer where the data were presented. “It means that those patients who were going to start osimertinib had the same QoL as the general population. During treatment, what we saw was that this QoL was practically maintained in all of the domains [analyzed]. This treatment, compared with placebo, did not impact patient QoL.”
In December 2020, the FDA approved the third-generation EGFR TKI osimertinib for the adjuvant treatment of patients with NSCLC whose tumors harbor EGFR exon 19 deletions(Ex19del) or exon 21 L858R mutations following surgical resection.3 The approval was based on results from ADAURA, in which osimertinib demonstrated a clinically meaningful and statistically significant disease-free survival (DFS) benefit compared with placebo (HR, 0.20; 99.12% CI, 0.14-0.30; P <.0001).
The double-blind, phase 3 study enrolled 682 adult patients who had undergone complete surgical resection for stage IB, II, or IIIA EGFR-mutant NSCLC. To be eligible for enrollment, patients had to be aged 18 years and older or 20 years and older, if they were from Japan and Taiwan. Patients needed to have confirmed primary nonsquamous disease and be positive for exon 19 deletions or exon 21 L858R deletion. An MRI or CT scan of the brain were required prior to undergoing randomization or surgery. Additionally, surgical resection needed to be completed with negative margins.
Patients were randomized 1:1 to receive either 80 mg of osimertinib once daily or placebo once daily for 3 years or until recurrence or discontinuation. The primary end point of the study was DFS in those with stage II and IIIA disease, with key secondary end points consisting of DFS in the overall population, landmark analysis of DFS, overall survival, safety, and HRQoL.
In the adjuvant setting, HRQoL is an important clinical consideration for patients who have undergone surgery with curative intent, are free of disease, and are in need of long-term treatment is reduce the risk of recurrence. Regarding adjuvant treatment, the goal is to improve outcomes, while maintaining HRQoL.
For the analysis, patients were asked to complete the SF-36 questionnaire at baseline, 12 weeks, and 24 weeks, followed by every 24 weeks thereafter until treatment completion, treatment discontinuation, or disease recurrence. Patient outcomes were evaluated for 8 individual SF-36 health domains and 2 aggregated summary scores.
The 8 domains included in the analysis were physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health, while the summary scores included PCS and MCS. The survey was scored through a norm-based scoring relative to the 2009 US general population, which yielded T-scores. Higher T-scores were indicative of better health, with the general population having a mean score of 50.
Investigators utilized a mixed model of repeated measures (MMRM) to analyze changes in SF-36 scoring from baseline through week 96. TTD was defined as the time from date of pre-dose randomization to the date of the first confirmed clinically important worsening, which was confirmed at a subsequent assessment or death.
“In the ADAURA trial, patients were asked out to fill out PRO questionnaires,” Majem explained. “[These] are questionnaires that aren’t used in patients who don't have cancer [but] in those who are in normal condition. This is a questionnaire that evaluates functional, physical, and psychological conditions of patients. It's a very [broad] questionnaire that gave us a lot of information on all these domains.”
Although the questionnaires were not cancer-specific, SF-36 has been used to assess HRQoL over a period of 4 weeks in patients who are cancer free following surgery.
Additional data indicated that health domain T-scores were comparable between patients who received osimertinib and those who received placebo. Most patients were comparable with the general population (within ±0.3 DR of the normative mean). However, investigators noted lower T-scores in role-physical, social functioning, and role-emotional domains (0.4-0.9 SD below the normative mean).
MMRM adjusted mean change in SF-36 health domain T scores for patients who were treated with osimertinib included 0.53 (95% CI, -0.10-1.16) for physical functioning, 2.67 (95% CI, 1.91-3.43) for role-physical, 1.66 (95% CI, 0.91-2.40) for bodily pain, -0.41 (-1.12-0.31) for general health, 0.98 (95% CI, 0.22-1.74) for vitality, 2.77 (95% CI, 2.06-3.49) for social functioning, 1.05 (95% CI, 0.22-1.87) for role-emotional, and 1.17 (95% CI, 0.44-1.90) for mental health.
In the placebo arm, changes included 1.38 (95% CI, 0.74-2.03) for physical functioning, 4.47 (95% CI, 3.69-5.25) for role-physical, 2.22 (95% CI, 1.45-2.99) for bodily pain, 1.09 (95% CI, 0.36-1.83) for general health, 2.91 (95% CI, 2.13-3.69) for vitality, 3.88 (3.14-4.62) for social functioning, 2.51 (95% CI, 1.66-3.36) for role-emotional, and 2.05 (95% CI, 1.30-2.80) for mental health.
Data from the PROs analysis further support adjuvant osimertinib as a novel treatment strategy in patients with EGFR-positive disease, concluded Majem.
1. Majem M, Goldman JW, John T, et al. Patient-reported outcomes from ADAURA: osimertinib as adjuvant therapy in patients with resected EGFR mutated (EGFRm) NSCLC. Abstract presented at: 2020 World Conference on Lung Cancer; January 28-31, 2021; Virtual. Accessed January 29, 2021. https://bit.ly/3aePvTN
2. Additional ADAURA analyses help support the benefit of adjuvant osimertinib in patients with resected EGFR-mutated NSCLC. News release. IASLC. January 27, 2021. Accessed January 29, 2021. http://bit.ly/3oxgkaE
3. FDA approves osimertinib as adjuvant therapy for non-small cell lung cancer with EGFR mutations. News release. December 18, 2020. Accessed January 29, 2021. http://bit.ly/2KE54v6