The prognostic value of patient reported outcomes (PROs) and clinical/demographic variables in the CASPIAN study.

Apar Kishor Ganti University of Nebraska Medical Center, Omaha, NE info_outline Apar Kishor Ganti, Sukhvinder Johal, Daniel Jackson, Nenad Medic, Kieran Davey, Lance Brannman

Authors Apar Kishor Ganti University of Nebraska Medical Center, Omaha, NE info_outline Apar Kishor Ganti, Sukhvinder Johal, Daniel Jackson, Nenad Medic, Kieran Davey, Lance Brannman Organizations University of Nebraska Medical Center, Omaha, NE, AstraZeneca, Cambridge, United Kingdom, AstraZeneca, Gaithersburg, MD Abstract Disclosures Research Funding Pharmaceutical/Biotech Company AstraZeneca Background: PROs have been shown to predict outcomes in non-small cell lung cancer and, using the FACT-G PRO instrument, in extensive stage small cell lung cancer (ES-SCLC). This study explored the relationships between EORTC QLQ-C30 domains and overall survival (OS) and progression free survival (PFS) in the phase III ES-SCLC CASPIAN trial, with and without adjustments for treatment (tx) and baseline clinical and demographic variables. Methods: CASPIAN had 3 treatment arms: durvalumab plus platinum–etoposide; durvalumab plus tremelimumab plus platinum–etoposide; and platinum–etoposide alone. It included the EORTC QLQ-C30, a PRO instrument consisting of 5 functioning scales (physical, role, emotional, cognitive, social), a global health status/quality of life (QoL) scale, 3 symptom scales (fatigue, nausea/vomiting, pain), 5 single item symptom assessments (dyspnea, insomnia, appetite loss, constipation, diarrhea) and a single financial difficulties item. Higher functional and QoL scores indicate better health status/function (anticipated positive OS/PFS associations) while higher symptom and financial difficulty scores represent a greater burden (anticipated negative OS/PFS associations). Baseline PRO scores were pooled across the 3 CASPIAN arms to obtain the most PRO information and used in 3 Cox proportional hazard models for OS and PFS: (A) scores only, (B) scores with a tx category for each CASPIAN arm, and (C) scores with tx categories and other baseline covariates (sex, age [ < 65, ≥65], ECOG performance status [0, > = 1], smoker [Y/N], CNS metastasis [Y/N], race [Asian, non-Asian], stage [III, IV], region [Asia, Europe, North and South America]). Models B and C were stratified by the type of platinum received. Backwards selection found the set of variables most associated with OS and PFS. There was no correction for multiplicity and nominal P-values < 0.05 were used to assess importance. Results: The outcomes and models associated with more favorable baseline PRO scale/item scores were: (i) better OS and PFS across all 3 Cox models [physical, role, social, QoL, fatigue, pain]; (ii) better OS [emotional (models A,C), nausea/vomiting (model C), dyspnea (model C)], and (iii) better PFS [emotional (model C), financial difficulties (models A,B,C)]. Among the 90 estimated Cox hazard ratios, 82 had the anticipated directions for OS and PFS with 54/90 of the estimates having P < 0.05. In each Cox model, more favorable baseline diarrhea scores were associated with reduced OS. All 15 baseline PRO score domains for OS and 10/15 for PFS were important in the stepwise selection process. Conclusions: The results largely indicate that baseline PROs had prognostic value in the CASPIAN trial across different specifications, some including tx and baseline clinical and demographic values. A better understanding of the relationship between tx and PROs may aid tx decisions. Clinical trial information: NCT03043872.