Patient‐reported outcomes as a prognostic marker of survival in patients with advanced nonsmall cell lung cancer treated with immunotherapy

Abstract

There has been minimal research on the prognostic value of patient-reported outcomes (PROs) for immune checkpoint inhibitors (ICIs). The relative performance of PROs compared to established markers such as Eastern Cooperative Oncology Group Performance Status (ECOG-PS) and the Lung Immune Prognostic Index (LIPI) is unknown. In our study, data from the advanced nonsmall cell lung cancer (NSCLC) single-arm atezolizumab trials BIRCH, FIR and randomised-trials OAK, POPLAR (atezolizumab vs docetaxel) were pooled. The study included 1548 participants who initiated atezolizumab. The associations between pretreatment PROs and overall survival (OS) and progression-free survival (PFS) were modelled using Cox proportional hazards regression. Prediction performance was assessed using the C-statistic (c). PROs were recorded via the EORTC QLQ-C30 and QLQ-LC13. Patient-reported physical function, fatigue, global health, appetite, role function, pain, dyspnoea, social function, constipation, nausea-vomiting, emotional function and coughing were significantly associated with OS and PFS on univariable and adjusted analysis (P < .05). Physical function (c = 0.654), fatigue (c = 0.653) and global health (c = 0.650) were the most predictive variables for OS. Comparatively, the OS prediction performance of physical function (c = 0.65) was superior to ECOG-PS (c = .59) and LIPI (c = 0.63). On multivariable analysis physical function, ECOG-PS and LIPI were all significant (P < .001). In conclusion, PROs were identified as independent prognostic factors for OS and PFS in advanced NSCLC patients receiving ICI therapy. Further, patient-reported physical function was more predictive of OS than ECOG-PS and LIPI and contained independent information. This highlights the value of PROs as prognostic and stratification factors for clinical use and research trials of ICIs.

Integrative evaluation of primary and metastatic lesion spectrum to guide anti-PD-L1 therapy of non-small cell lung cancer: results from two randomized studies

“… 11 As for stability, the primary and metastatic lesion spectrum would not be disturbed by the short-term physical condition, whilst hematological markers (e.g. LIPI 7 , 8 and CRP 10 ) might be affected by infection, trauma, and the usage of glucocorticoids or antibiotics, etc. As regards objectivity, the baseline metastatic lesion number and the metastatic sites would not be interfered by subjective judgment, as compared with patient-reported outcomes.…”

“…As regards objectivity, the baseline metastatic lesion number and the metastatic sites would not be interfered by subjective judgment, as compared with patient-reported outcomes. 10 Even so, we believe that the combination of multi-dimensional information would be the mainstay of future precision medicine, and the primary and metastatic lesion spectrum might serve as another dimension to complement with the identified markers.…”

“… 3 , 4 Thus, numerous parameters predicting ideal candidates for second-line ICI treatment have been identified as potential markers, 5 encompassing body mass index (BMI), 6 neutrophil and lymphocyte count number (LIPI), 7 , 8 C-reactive protein (CRP), 9 patient-reported physical function. 10 Still, efforts to establish effective markers from other dimensions, specially from image examinations, 11 are warranted to complement the field and promote precision medicine.…”

Patient-Reported Outcomes Predict Progression-Free Survival of Patients with Advanced Breast Cancer Treated with Abemaciclib

“…In cancer clinical trials, PROs are an important secondary outcome for establishing the effectiveness of treatments [2][3][4][5]. More recently, a range of PROs have been found to be prognostic of cancer outcomes [6][7][8][9][10][11][12][13][14][15], potentially even more so than common clinicopathological data or established metrics such as the physician assessed Eastern Cooperative Oncology Group Performance Status (ECOG-PS) [10,16,17]. Although it is still unclear whether the prognostic importance differs significantly between treatments and cancers, and whether PROs can predict treatment efficacy in addition to prognosis [7,8,10].…”

“…More general to ABC, pre-treatment PROs have been shown to be prognostic of PFS in patients initiating chemotherapy options [27,28]. PROs have also shown to be associated with PFS in other cancer types [6][7][8][9][10][11][12][13][14][15]. However, as the importance of prognostic variables can differ vastly between received treatments and cancer types, there is a need to evaluate PROs for CDK 4/6 inhibitors specifically.…”