Outcomes of temozolomide and capecitabine chemotherapy used in neuroendocrine and endocrine tumours: A real-world comparison of treatment evidence in Alberta, Canada, from 2011-2021.

Abstract

e23064 Background: Capecitabine and temozolomide (CAPTEM) have proven effective in improving progression-free survival (PFS) in pancreatic neuroendocrine tumors (PNETs). This study extends its evaluation to determine efficacy across the broader spectrum of neuroendocrine and endocrine tumors (NETs and ETs) Methods: This was a retrospective cohort study, for which REB approval was obtained. We identified all patients with NETs & ETs treated with CAPTEM (at least 1 cycle) in Alberta from 2011-2021. PFS & OS from start of CAPTEM were compared between groups stratified by primary: Pancreatic NETs (PNETs); gastrointestinal NETs (GINETs); Pulmonary NETs (PuNET); other NETs (ONETs). Among 159 patients identified, there were 67 PNETs, 38 GINETs, 35 PuNETs, & 19 ONETs. PFS & OS were compared between NETs when CAPTEM was used as 1st vs. later-line therapy & patients receiving ≥ 6 vs. < 6 cycles. Kaplan-Meier & Log- Rank tests were used, adjusted for age & sex using cox regression. Results: Compared to PNETs, GINETs demonstrated no statistically significant difference in median progression-free survival (PFS 10.5 vs 9 m, p = 0.11; HR = 1.14 95%CI = 0.76-1.71; HR adjusted for age & sex = 1.10, 95% CI = 0.79 -1.65) and overall survival (OS median 15.9 vs 19 months, p = 0.15; HR = 1.13 , 95% CI = 0.69 -1.85, HR adjusted to age and sex = 1.11 , 95% CI = 0.69 - 1.81). Conversely, PuNETs & ONETs were associated with significantly lower median PFS (PuNETs 3 vs 9m, p = 0.02, HR = 1.6 95%CI = 1.1 -2.4, HR adjusted for age & sex = 1.65, 95% CI = 1.15 - 2.5); ONETs 2 vs 9m, p = 0.01, HR = 1.56 95%CI = 1.1 -2.6, HR adjusted for age &sex = 1.59, 95% CI = 1.14 -2.7) and OS (PuNETs 6.8 vs 19 m, p = 0.01, HR = 1.7, 95% CI = 1.06 - 2.7, HR adjusted to age & sex = 1.73, 95% CI = 1.08 to 2.71); ONETs 5.6 vs 19 m, p = 0.02, HR = 1.49, 95% CI = 1.1 - 2.7, HR adjusted to age and sex = 1.51, 95% CI = 1.05 - 2.8). OS analyses revealed comparable trends.CAPTEM therapy administered as 1st-line treatment was associated with longer median PFS & OS compared to later-line use. PFS (10 vs 3.5m, P = .008; HR = 0.56 95% CI = 0.40 -0.78) & OS (23 vs 4.7m, P = 0.0001; HR = 0.42 95% CI = 0.29 -0.62). Additionally, patients receiving ≥6 cycles of CAPTEM exhibited higher median PFS and OS compared to those receiving < 6 cycles. PFS (18 vs 2m, P = 0.0001; HR = 0.22 95%CI = 0.16 - 0.32) & OS (29 vs 4.2m, P = 0.0001; HR = 0.22 95% CI = 0.14 - 0.34). Conclusions: CAPTEM therapy demonstrates comparable efficacy in gastrointestinal NETs (GINETs) to that observed in pancreatic NETs (PNETs) but appears to be less effective in non- gastroenteropancreatic NETs and Endocrine tumors. Importantly, the use of CAPTEM as a first- line treatment and the administration of an extended cycle regimen are significantly associated with improved progression free survival (PFS) and overall survival (OS) across the broader NET spectrum, representing a novel prognostic variable not previously reported.