Journal
LUNG CANCER
Volume 166, Issue -, Pages 255-264Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.lungcan.2021.11.018
Keywords
Non-small cell lung cancer; EGFR mutations; Gefitinib; Tremelimumab; Combination; Phase I trial
Categories
Funding
- Gustave Roussy cancer campus
- Foundation Gustave Roussy
- SIRIC SOCRATE [INCa DGOS INSERM 6043]
- SIRIC SOCRATE 2.0 [INCa-DGOS-INSERM_12551]
- MMO program [ANR-10IBHU-0001]
- Direction Generale de l'Offre de Soins (DGOS) [TRANSLA 12-174]
- Institut National du Cancer (INCa) [2012-062 N_Canceropole: 2012-1-RT-14-IGR-01]
- Gustave Roussy
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This study evaluated the safety and efficacy of the combination of tremelimumab and gefitinib in patients with EGFR-mutant NSCLC. The results showed limited efficacy with this combination, with stable disease being the best overall response in most patients. Gastrointestinal toxicity was the main adverse reaction.
Introduction: A phase I open-label multicentre study was initiated to evaluate the association of tremelimumab with gefitinib in EGFR-mutant NSCLC patients who progressed after first-generation EGFR-TKI. Here we provide the efficacy data from the entire cohort. Material and methods: Patients with advanced EGFR-mutant NSCLC with progression after response to EGFR-TKI were enrolled. Study treatment was gefitinib 250 mg daily and tremelimumab at 3 dose levels: 3, 6 and 10 mg/kg IV Q4W for 6 cycles followed by Q12W until progression or unacceptable toxicity. The primary objective was safety and tolerability, and to establish a RP2D. Results: Between January 2014 and July 2015, 27 patients (21 in the escalating dose cohort and 6 in expansion cohort) received at least one dose of tremelimumab. DLTs occurred in 4 patients: 1 at 3 mg/kg (one grade 3 diarrhoea), 1 at 6 mg/kg (one grade 3 diarrhoea) and 2 at 10 mg/kg (one grade 3 diarrhoea and one grade 3 AST/ALT increase) of tremelimumab. Grade 3 TRAE occurred in 22 patients (81%), most frequently diarrhoea (30%) and ALT/AST increase (15%). Stable disease was the best overall response in 72% patients, with median PFS of 2.2 months (95% CI, 1.8-4.2). All patients discontinued treatment, most frequently due to disease proogression (63% of patients). Conclusion: The recommended dose of tremelimumab in combination with gefitinib in EGFR-mutant NSCLC patients was 3 mg/kg. The gastrointestinal toxicity and the limited efficacy data prevented further evaluation of this combination. (GEFTREM; clinical trial number NCT02040064)
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