Abstract 9P
Background
In FLAURA2 (NCT04035486), 1L osi + platinum-pemetrexed (pem) chemotherapy (CTx) (n=279) significantly improved PFS vs osi alone (n=278) in EGFRm advanced NSCLC (HR 0.62; 95% CI 0.49, 0.79; p<0.0001 per investigator). Safety of osi + CTx was consistent with individual Tx profiles and was associated with higher incidence of G≥3 AEs vs osi. Most G≥3 AEs occurred during platinum-based CTx induction phase (pem + platinum CTx, 4 cycles Q3W) but reduced during maintenance. We report FLAURA2 PROs.
Methods
Symptoms, function and HRQoL were measured using EORTC QLQ-C30/LC13 questionnaires (Table). Score (range 0–100) changes from baseline (BL) to progression/19 mos were analysed by a mixed-effects model. A clinically meaningful within-pt change was defined as ≥10 point change from BL. Tolerability was assessed with PRO-CTCAE items.
Results
EORTC questionnaire completion/PRO-CTCAE visit compliance was ≥80/≥75% to Wk 82. Non-clinically meaningful improvements in global health status/quality of life (GHS/QoL) and physical function were seen in both arms: average least-squares mean (LSM) change in GHS/QoL from BL (95% CI) over all visits was 3.32 (1.67, 4.98) with osi + CTx and 7.38 (5.70, 9.07) with osi. Non-clinically meaningful worsening of fatigue/appetite loss (LSM change from BL [95% CI]) was seen with osi + CTx in induction (10 wks: 2.98 [0.65, 5.32]/9.30 [6.13, 12.46]), but improved during maintenance (28 wks: -0.33 [-2.66, 2.00]/5.52 [2.60, 8.44]). A trend to improvement in dyspnoea, chest pain and cough was seen in both arms; clinically meaningful improvement for cough from Wks 5 (osi + CTx) and 6 (osi). PRO-CTCAE results showed osi + CTx and osi were similarly well tolerated except nausea/vomiting (more common with osi + CTx).
Conclusions
A trend to improved HRQoL and several symptoms was seen after induction CTx. Negative changes in HRQoL from adding CTx to osi were not clinically meaningful and were mostly transient (trended back to BL post-induction CTx). Table: 9P
| Median total study drug exposure, mos (range) at data cut-off 3 Apr 2023Osi + CTx: Platinum CTx, 2.8 (0.7, 4.1); Pem, 8.3 (0.7, 33.8); Osi, 22.3 (0.1, 33.8)Osi alone: 19.3 (0.1, 33.8) | ||
| PRO tool | Prespecified primary scales | Schedule |
| EORTC QLQ-C30 | GHS/QoL, physical function, fatigue, appetite loss | BL, Q3W to Wk 10 & Q6W to second-PFS (PFS2) |
| EORTC QLQ-LC13 | Cough, dyspnoea, chest pain | BL, QW to Wk 10 & Q3W to PFS2 |
| PRO-CTCAE (exploratory endpoint) | Mouth/throat sores, nausea, vomiting, diarrhoea, abdominal pain, loss of bowel movement control, dry skin, hair loss, numbness/tingling in hands/feet |
Change from BL: increased GHS/QoL = improved GHS/QoL & function; decreased symptom score = improved symptom burden
Clinical trial identification
NCT04035486.
Editorial acknowledgement
The authors would like to acknowledge Kiara Whelan, BSc, of Ashfield MedComms, an Inizio Company, for medical writing support that was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
C.K.K. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Takeda, Pfizer, Novartis, GSK, Merck KGA, Roche, Janssen, MSD; Financial Interests, Institutional, Research Grant: AstraZeneca, Amgen, Roche, Merck KGA. K. Laktionov: Other, Personal and Institutional, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Roche AG, Biocad; Other, Personal and Institutional, Advisory Board: AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Roche AG, Biocad, Pfizer; Other, Personal and Institutional, Funding: AstraZeneca; Other, Personal and Institutional, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Roche AG, Biocad. S. Kim: Other, Personal and Institutional, Invited Speaker: Boehringer Ingelheim; Other, Personal and Institutional, Advisory Board: Terapex; Other, Personal and Institutional, Principal Investigator: Yuhan; Other, Personal and Institutional, Advisory Role: AstraZeneca, Amgen, Boehringer Ingelheim, Daiichi Sankyo, Janssen, Takeda. T. Kato: Financial Interests, Personal, Full or part-time Employment, Family Member: Lilly; Financial Interests, Institutional, Research Grant: Chugai Pharma, Merck Sharp & Dohme, Pfizer, AstraZeneca, Lilly, AbbVie, Regeneron, Novartis, Amgen, Merck KGaA, Takeda, Haihe Biopharma, Blueprint Medicines, Turning Point Therapeutics, Daiichi Sankyo, BeiGene; Financial Interests, Personal, Advisory Role: AstraZeneca, MSD, Pfizer, Merck Serono, BeiGene, Novartis, Daiichi Sankyo, Janssen; Financial Interests, Personal, Other, Honoraria: Chugai Pharma, Ono Pharmaceutical, Lilly, AstraZeneca, Taiho Pharmaceutical, Pfizer, Merck Sharp & Dohme, Novartis, Takeda, Daiichi Sankyo, GSK, Amgen, Merck KGaA, BeiGene, Boehringer Ingelheim, Janssen. P. Mitchell: Financial Interests, Personal and Institutional, Advisory Board: Amgen, AstraZeneca, BMS, Roche, MSD, Novartis, Pfizer; Financial Interests, Personal and Institutional, Advisory Role: Grey Wolf; Other, Personal and Institutional, Other, Coordinating Investigator: AstraZeneca, Amgen. S. Kuyama: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Other, Institutional, Principal Investigator: AstraZeneca. F.A. Shepherd: Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca; Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca, Lilly; Financial Interests, Institutional, Funding: AstraZeneca/MedImmune, Squibb, Lilly, Roche Canada, Pfizer. L. Poole: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca, Lilly, Takeda. M. Albayaty: Financial Interests, Institutional, Full or part-time Employment: AstraZeneca; Financial Interests, Institutional, Stocks/Shares: AstraZeneca. N.P. Amin: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. K. Kobayashi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda Pharmaceutical Co.; Financial Interests, Personal, Expert Testimony: Daiichi Sankyo Co. J.E. Gray: Other, Personal, Advisory Board, Consultant / Advisor: AbbVie, AstraZeneca, Blueprint Medicines, Daiichi Sankyo, Inc, EMD Serono, Gilead Sciences, Inc, IDEOlogy Health, Janssen Scientific Affairs, LLC, Jazz Pharmaceuticals, Loxo Oncology Inc, Merck & Co, Inc, Novartis, OncoCyte Biotechnology, Spectrum ODAC, Takeda Pharmaceuticals, Triptych Health Partners; Other, Personal, Officer, Chair: SWOG Lung Committee; Other, Personal, Member of Board of Directors: IASLC Board of Directors Member; Other, Personal, Full or part-time Employment: Moffitt Cancer Center; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Genentech, G1 Therapeutics, Ludwig Institute of Cancer Research, Merck & Co, Inc, Novartis, Pfizer; Other, Personal and Institutional, Leadership Role, Ex-Chair: ASCO Education Committee; Other, Personal and Institutional, Leadership Role, Chair: SWOG Lung Committee; Other, Personal and Institutional, Other: AbbVie, AstraZeneca, Blueprint Medicines, Daiichi Sankyo, Inc, EMD Serono, Gilead Sciences, Inc, IDEOlogy Health, Janssen Scientific Affairs, LLC, Jazz Pharmaceuticals, Loxo Oncology Inc, Merck & Co, Inc, Novartis, OncoCyte Biotechnology, Spectrum ODAC, Takeda Pharmaceuticals, Triptych Health Partners. All other authors have declared no conflicts of interest.