A comparative study evaluating the quality of life in patients receiving chemotherapy versus oral TKI in the third line and beyond setting for advanced non–small-cell lung cancer.
Authors: Menon Nandini Sharrel , Noronha Vanita , Patil Vijay Maruti , Singh Ajaykumar Chandrabhan , Purandare Nilendu , Mahajan Abhishek , Janu Amit , More Sucheta , Goud Supriya , Shah Srushti , Jobanputra Kunal Naishadh , Karuvandan Naveen , Sarma Rup Jyoti , Patel Dhwani , Joarder Ritam , SHAH DARSHIT KALPESHKUMAR , Shah Minit Jalan , John Anupa , Kumar Prashant , Prabhash Kumar 
Published: June 2023

e21195

Background: The outcomes in advanced non-small cell lung cancer (NSCLC) have improved due to the availability of more effective systemic & improved supportive care. This has increased the number of patients who seek treatment in the third line & beyond setting. We conducted this study to compare the quality of life (QoL), toxicity & outcomes in patients receiving chemotherapy & oral tyrosine kinase inhibitors (TKIs) in this setting. Methods: In this phase 3 randomized open-label study patients with stage III/IV NSCLC with disease progression on at least 2 prior lines of chemotherapy, with a life expectancy of at least 3 months, without prior TKI exposure, and stable brain metastases (if any) were included. Patients were randomised to receive chemotherapy(Gemcitabine/docetaxel/paclitaxel/vinorelbine) or TKI (erlotinib or gefitinib). Patients were evaluated at every visit for clinical benefit and toxicity (as per CTCAE v4.3). A radiological tumour response assessment was done every 8-12 weeks from the start of therapy. The QoL was assessed using the EORTC QLQ C-30 & LC-13 questionnaires at baseline and every 8-10 weeks while on treatment. The primary endpoint is the change in QoL scores at 8-10 weeks, the secondary endpoints are safety and overall survival. The change in QoL scores at baseline and scores at 8-10 weeks was determined and the mean difference between the arms was compared using the independent t-test. Overall and progression-free survival was determined using the Kaplan-Meier method and Cox proportional regression analysis. Results 246 patients were enrolled in the study, 123 in each arm. There was a male predominance in both arms. There was no significant difference in the change in the QoL scores from baseline to the subsequent visit (at 8-10 weeks) in both arms in all domains of QLQ C-30 & LC 13 except alopecia. The mean difference in scores for alopecia was 23.73 (+/-52.22) in the chemotherapy arm & -18.35 (+/- 47.32) in the oral TKI arm (p = 0.000). The median follow-up was 88.1 mos (95%CI39.04-137.15). On ITT analysis the median progression-free survival (PFS) was 3.13 mos (95%CI 2.15-4.11) in the chemotherapy arm and 2.26 mos (95%CI 2.1-2.43) in the oral TKI arm, hazard ratio (HR) 1.074 (95% CI 0.833- 1.38), p = 0.6. There were 120 deaths in each arm. The median overall survival (OS) was 7.63 mos (95% CI 5.96-9.30) in the chemotherapy arm and 7.5 mos in the oral TKI arm (95% CI 5.85-9.14); HR 1.024 (95%CI 0.793-1.321),p = 0.9. The toxicity profile was similar in both arms except for CIPN, alopecia, pedal edema which was higher in the chemotherapy arm, & dry skin & skin rash was higher in the oral TKI arm Conclusion In the third line setting there is no significant difference in most QoL domains with similar outcomes( PFS& OS) and toxicity profile is consistent with expected toxicities of the drugs.