Afatinib in patients with solid tumors with neuregulin 1 (NRG1) fusions: a case series from the Targeted Agent and
J Rodon1, M Rothe2, P K Mangat2
1Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, USA.
Background:
TAPUR is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and targetable genomic alterations. Results of four patients with various tumors with NRG1 fusions treated with afatinib are reported.
Patients And Methods:
Eligible patients had advanced cancer, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with NRG1 fusions, and no standard treatment options. The primary endpoint was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks' duration (SD16+). Secondary endpoints included OR, duration of response, duration of SD, and safety.
Results:
Four patients were enrolled from February 2020 to July 2021; all had solid tumors [colorectal cancer (n = 2), non-small-cell lung cancer (n = 1), and pancreatic adenocarcinoma (n = 1)] with an NRG1 fusion. All patients were evaluable for efficacy. One partial response and two SD16+ were observed. One patient was still alive as of October 2024 with SD of 134 weeks' duration. No patients had a drug-related grade 3-5 adverse event (AE) or serious AE.
Conclusion:
Though the sample size was small, afatinib demonstrated promising activity in patients with advanced solid tumors with NRG1 fusions, including durable DC warranting additional study.
Insights
Afatinib showed promising antitumor activity in patients with advanced solid tumors harboring NRG1 fusions. This targeted therapy achieved durable disease control, suggesting potential for further clinical investigation.
Area of Science:
- Oncology
- Genomics
- Targeted Therapy
Background:
- The TAPUR trial is a phase II basket study assessing targeted agents in advanced cancers with genomic alterations.
- This report focuses on four patients with NRG1 fusion-positive tumors treated with afatinib.
Purpose of the Study:
- To evaluate the antitumor activity of afatinib in patients with advanced solid tumors and NRG1 fusions.
- To assess disease control, objective response, duration of response, and safety.
Main Methods:
- Four patients with advanced solid tumors (colorectal, non-small-cell lung, pancreatic) and NRG1 fusions were enrolled.
- Eligibility included measurable disease, ECOG 0-2, adequate organ function, and no standard treatment options.
- Disease control (DC) was the primary endpoint, defined as objective response or stable disease of at least 16 weeks (SD16+).
Main Results:
- One partial response and two instances of SD16+ were observed among the four evaluable patients.
- One patient achieved durable stable disease for 134 weeks and remained alive.
- No drug-related grade 3-5 adverse events or serious adverse events were reported.
Conclusions:
- Afatinib demonstrated promising antitumor activity and durable disease control in this small cohort.
- These findings support further investigation of afatinib for advanced solid tumors with NRG1 fusions.
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