P50.10 Intravenous (IV) versus IV/oral route of etoposide administration: impact on real-world SCLC survival outcomes

Abstract

Platinum-etoposide doublet (PE) is the recommended first-line (1L) chemotherapy for small cell lung cancer (SCLC). Evidence shows that oncology patients prefer oral treatment to IV. This study compared outcomes between 1L intravenous (IV), and IV followed by oral (IV/oral) route of etoposide administration in real-world SCLC patients in Alberta, Canada. SCLC patients who were diagnosed between 2010 and 2016 and completed 1L etoposide at an academic tertiary cancer centre, (Tom Baker Cancer Centre) were included. Data were retrieved from the Glans-Look database excluding those with mixed histology. Outcomes explored included, a] overall survival, (OS), the time in months from diagnosis date to death/last contact, b] tumor objective response rate (ORR), the complete and partial responses as defined by the RECIST v1.1 criteria, using diagnostic imaging reports within 4-8 weeks post 1L or as reported in oncologist progress notes, and c] 1L-related toxicity rate, derived from progress notes, graded using the CTCAE criteria (version 5). Also measured was the progression free survival (PFS): time difference in months from diagnosis date to first progression post 1L or death, whichever occurs first. Comparison between IV/oral and IV groups was performed using Fisher’s Exact (point estimates), Log-Rank tests (Kaplan-Meier survival estimates) and Cox proportional hazard model (survival outcome predictors). A priori statistical significance was p < 0.05. Analyses were performed using SPSS statistical software (version 25). There were 222 patients, 1L was mostly PE [93%] employing etoposide in combination with cisplatin [61%] or carboplatin [32%]. 168 [76%] were IV/oral group. Median age was 66 years, 132 [60%] female, and 138 [62%] had extensive stage SCLC (ES). Performance status (ECOG) was 0-2 in 112 (51%), ≥3 in 9 (4%) and unknown in 101 (46%) patients. IV and IV/oral patients have similar characteristics, but compared to IV/oral, the IV group had less limited stage disease (LS), [p=0.28]. 100 patients experienced grade 3 or 4 toxicities, mainly neutropenia [83%]. The rates were similar for IV/oral versus IV group, p= 0.36. Stratified by stage however, toxicity from IV was greater in LS than ES patients [60 vs 39%]. Overall, ORR for IV/oral versus IV group was 71% vs 66%, [p=0.85]. Within stage, ORR was 79 vs. 89% in LS [p< 0.01] and 58 vs 71% in ES [p=0.23], IV/oral relative to IV group. There was no statistically significant difference in PFS or OS with IV/oral relative to IV groups [PFS: 14 vs 12 months for LS; both 6 months for ES; OS: 32 vs 25 mo. for LS; 12 vs 14 mo. for ES]. Predictors of favorable survival include presence of grade 3 or 4 toxicity in LS [HR= 0.45, p=0.03] and second-line chemotherapy receipt in ES [HR= 0.46, p<0.01]. Consistent with previous reports, we found high oral treatment rate in real-world SCLC patients and no statistically significant differences in SCLC survival outcomes comparing IV/oral versus IV group. Future studies may explore why severe chemotherapy-related toxicity (grade 3 or 4) in LS patients predicts favorable survival.