Comparative Outcomes of Second-line Topoisomerase-I Inhibitor Therapies on Neuroendocrine Carcinoma

Abstract

Introduction: This investigation aims to assess the outcomes for second-line therapies to treat extrapulmonary neuroendocrine carcinoma (EP-NEC) after first-line platinum-based chemotherapy.

Methods: With IRB approval, we conducted a retrospective study of EP-NEC patients that progressed on first-line platinum chemotherapy from 2008 to 2018. Demographic data and treatment-related characteristics were collected and represented as descriptive statistics. The primary endpoints include overall survival (OS) and progression-free survival (PFS). OS and PFS were estimated and stratified by site of primary (gastroenteropancreatic [GEP] versus non-GEP) and type of second-line therapy (irino/topotecan versus others). Log-rank test and Kaplan-Meier curves were used to compare survival distributions between groups.

Results: Forty-seven patients met eligibility, with median age 65 (range 31-82), 62% male, and 83% White; 22 were GEP and 25 were non-GEP primary. Thirty patients (63.8%) received second-line therapy where 11 received irinotecan/topotecan (ir/to), while 19 received other agents (temozolomide, other platinum agents, gemcitabine, paclitaxel, pembrolizumab, and sunitinib). The median OS was 10.3 months in the ir/to group versus 13.4 months for other therapies, p = 0.10. The median PFS for ir/to therapy compared to other therapies was 2.0 months versus 1.8 months, respectively, p = 0.72. The OS and PFS with and without ir/to were not significantly different by the primary site (p = 0.61 and p = 0.21).

Discussion/conclusion: Many EP-NEC patients undergo second-line therapies. Interestingly, outcomes for ir/to-containing second-line therapies were not statistically different from other agents, regardless of the site of primary. With approval of new second-line therapies for small cell lung cancer, further research in therapeutic options is needed for this aggressive disease.

Keywords: Gastroenteropancreatic; Irinotecan; Neuroendocrine carcinoma; Neuroendocrine tumors; Topoisomerase inhibitors; Topotecan.

Figure 1.

Kaplan-Meier survival curves are shown above comparing irinotecan/topotecan-containing therapies (Ir/top) to other therapies without irinotecan or topotecan. A) The median OS was 10.3 months (95%CI, 2.9–22.6) in the ir/to group versus 13.4 months (95%CI, 10.1–20.5) for other therapies, p=0.10. B) The median PFS for ir/to therapy compared to other therapies was 2.0 months (95%CI, 0.3–2.4) versus 1.8 months (95%CI, 0.9–2.2), p=0.72. Log-rank tests were used to determine statistical significance.

Figure 1.

Kaplan-Meier survival curves are shown above comparing irinotecan/topotecan-containing therapies (Ir/top) to other therapies without irinotecan or topotecan. A) The median OS was 10.3 months (95%CI, 2.9–22.6) in the ir/to group versus 13.4 months (95%CI, 10.1–20.5) for other therapies, p=0.10. B) The median PFS for ir/to therapy compared to other therapies was 2.0 months (95%CI, 0.3–2.4) versus 1.8 months (95%CI, 0.9–2.2), p=0.72. Log-rank tests were used to determine statistical significance.

Figure 2.

A) Overall survival between GEP (N=22) versus non-GEP (N=25) tumors were similar, 10.7 (95%CI, 8.3–17.4) months versus 9.7 (95%CI, 7.6–14.7) months, p=0.60. B) Response to second-line chemotherapy was not significantly different regardless of primary site, with PFS for GEP tumors being 2.0 months (95%CI, 0.9–2.8) versus non-GEP tumors 1.5 months (95%CI, 0.3–2.0), p=0.21. Log-rank tests were used to determine statistical significance.

Figure 2.

A) Overall survival between GEP (N=22) versus non-GEP (N=25) tumors were similar, 10.7 (95%CI, 8.3–17.4) months versus 9.7 (95%CI, 7.6–14.7) months, p=0.60. B) Response to second-line chemotherapy was not significantly different regardless of primary site, with PFS for GEP tumors being 2.0 months (95%CI, 0.9–2.8) versus non-GEP tumors 1.5 months (95%CI, 0.3–2.0), p=0.21. Log-rank tests were used to determine statistical significance.