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Thomas William Lycan
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P48 - Small Cell Lung Cancer/NET - Chemo - IO (ID 236)
- Event: WCLC 2020
- Type: Posters
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P48.01 - Gemcitabine and Nivolumab for Subsequent Treatment of Metastatic Small Cell Lung Cancer (ID 3223)
00:00 - 00:00 | Presenting Author(s): Thomas William Lycan
- Abstract
Introduction
Small cell lung cancer (SCLC) represents a particularly aggressive neuroendocrine tumor with poor prognosis in the advanced stage and limited treatment options following progression with first line therapy. There is a particular need for novel therapeutic approaches within the refractory extensive stage population. Immunotherapy has seen relatively recent approval for treatment of relapsed or refractory SCLC, but overall response rates remain low. One approach to improve response rates is with the addition of cytotoxic chemotherapy to immune checkpoint inhibitors. Preclinical data support the use of gemcitabine as a potential synergistic combination with immunotherapy. Herein, we seek to identify if the addition of gemcitabine to nivolumab in second line therapy improves overall response rate while maintaining safety and improving progression free and overall survival.
Methods
We conducted a single-arm, open-label phase II trial using a Simon’s two-stage design to evaluate the combination of gemcitabine and nivolumab in patients with advanced stage SCLC who had relapsed or refractory disease following treatment with platinum-based chemotherapy. All patients had histologically confirmed SCLC and radiographically confirmed metastatic disease. Patients received gemcitabine 1000mg/m2 plus nivolumab 240 mg intravenously (G+N) every two weeks for at least four cycles. Treatment could be continued at the investigator’s discretion barring disease progression, unacceptable toxicity, or patient withdrawal from study. The primary outcome was radiographic response rate (RR) following four cycles of therapy, as compared to historical control of 10%. Secondary outcomes included overall survival (OS) and (PFS) from date of first treatment. Exploratory outcomes included peripheral immunophenotypic profiling of select patients to evaluate the impact of this combination on immune cells. Follow-up continued for just over a year (13.5 months) following first treatment.
Results
Fourteen participants were enrolled with a median age of 58 years old, 64% male, 86% white, with median 4.7 months since last platinum therapy, and 64% with prior immune checkpoint inhibitor therapy. One patient had a treatment response (1/14; 0.08, 95% confidence interval 0.0, 0.27). The study was stopped after completion of the first stage as only one response was observed and two were required to proceed to the second stage of the study. We observed a total of 8 deaths; median overall survival was 3.2 months following date of first treatment (95% CI 1.7,9.2 months). Eleven patients progressed; median progression-free survival was 1.8 months following date of first treatment (95% CI 1.6,8.6 months). Treatment-emergent adverse events (AEs) of any grade occurred in 12 participants (86%), with 6 (43%) having an AE that was grade 3-4. Treatment-related AEs occurred in 4 participants (most commonly cytopenias, elevated AST/ALT), only one of which was high grade (grade 3 lymphopenia). There were no AEs that caused death or treatment discontinuation.
Conclusion
Our study failed to prove a benefit with the combination of gemcitabine and nivolumab as it did not improve radiographic response rate as compared to historical control. PFS and OS were not prolonged with this treatment regimen.
