Dataset Information

Therapeutic Potential of Afatinib in NRG1 Fusion-Driven Solid Tumors: A Case Series.

ABSTRACT:

Background

Neuregulin 1 (NRG1) fusions, which activate ErbB signaling, are rare oncogenic drivers in multiple tumor types. Afatinib is a pan-ErbB family inhibitor that may be an effective treatment for NRG1 fusion-driven tumors.

Patients and methods

This report summarizes pertinent details, including best tumor response to treatment, for six patients with metastatic NRG1 fusion-positive tumors treated with afatinib.

Results

The six cases include four female and two male patients who ranged in age from 34 to 69?years. Five of the cases are patients with lung cancer, including two patients with invasive mucinous adenocarcinoma and three patients with nonmucinous adenocarcinoma. The sixth case is a patient with colorectal cancer. NRG1 fusion partners for the patients with lung cancer were either CD74 or SDC4. The patient with colorectal cancer harbored a novel POMK-NRG1 fusion and a KRAS mutation. Two patients received afatinib as first- or second-line therapy, three patients received the drug as third- to fifth-line therapy, and one patient received afatinib as fifteenth-line therapy. Best response with afatinib was stable disease in two patients (duration up to 16 months when combined with local therapies) and partial response (PR) of >18 months in three patients, including one with ongoing PR after 27 months. The remaining patient had a PR of 5 months with afatinib 40 mg/day, then another 6 months after an increase to 50 mg/day.

Conclusion

This report reviews previously published metastatic NRG1 fusion-positive tumors treated with afatinib and summarizes six previously unpublished cases. The latter include several with a prolonged response to treatment (>18 months), as well as the first report of efficacy in NRG1 fusion-positive colorectal cancer. This adds to the growing body of evidence suggesting that afatinib can be effective in patients with NRG1 fusion-positive tumors.

Key points

NRG1 fusions activate ErbB signaling and have been identified as oncogenic drivers in multiple solid tumor types. Afatinib is a pan-ErbB family inhibitor authorized for the treatment of advanced non-small cell lung cancer that may be effective in NRG1 fusion-driven tumors. This report summarizes six previously unpublished cases of NRG1 fusion-driven cancers treated with afatinib, including five with metastatic lung cancer and one with metastatic colorectal cancer. Several patients showed a prolonged response of >18 months with afatinib treatment. This case series adds to the evidence suggesting a potential role for afatinib in this area of unmet medical need.

SUBMITTER: Cadranel J

PROVIDER: S-EPMC7794194 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Therapeutic Potential of Afatinib in NRG1 Fusion-Driven Solid Tumors: A Case Series.

Cadranel Jacques J Liu Stephen V SV Duruisseaux Michaël M Branden Eva E Goto Yasushi Y Weinberg Benjamin A BA Heining Christoph C Schlenk Richard F RF Cheema Parneet P Jones Martin R MR Drilon Alexander A Trombetta Domenico D Muscarella Lucia Anna LA Tolba Khaled K Gounant Valerie V Cseh Agnieszka A Solca Flavio F Laskin Janessa J JJ Renouf Daniel J DJ

The oncologist 20200923 1

<h4>Background</h4>Neuregulin 1 (NRG1) fusions, which activate ErbB signaling, are rare oncogenic drivers in multiple tumor types. Afatinib is a pan-ErbB family inhibitor that may be an effective treatment for NRG1 fusion-driven tumors.<h4>Patients and methods</h4>This report summarizes pertinent details, including best tumor response to treatment, for six patients with metastatic NRG1 fusion-positive tumors treated with afatinib.<h4>Results</h4>The six cases include four female and two male pat ...[more]

PMID: 32852072

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Project description:Immunotherapy has revolutionized the treatment of both hematological malignancies and solid tumors. The use of immunotherapy has improved outcome for patients with cancer across multiple tumor types, including lung, melanoma, ovarian, genitourinary, and more recently breast cancer with durable responses seen even in patients with widespread metastatic disease. Despite the promising results, immunotherapy still helps only a subset of patients due to overall low response rates. Moreover, the response to immunotherapy is highly cancer specific and results have not been as promising in cancers that are considered less immunogenic. The strategies to improve immunotherapy responses have focused on biomarker selection, like PD-L1 status, and usage of combinatorial agents, such as chemotherapy, targeted therapy, and radiotherapy. Of particular interest, DNA-damaging agents have the potential to enhance the response to immunotherapy by promoting neoantigen release, increasing tumor mutational burden, and enhancing PD-L1 expression. Poly-ADP-ribose polymerase (PARP) inhibitors are one such class of drugs that has shown synergy with immunotherapy in preclinical and early clinical studies. PARP-based therapies work through the inhibition of single-strand DNA repair leading to DNA damage, increased tumor mutational burden, making the tumor a more attractive target for immunotherapy. Of the solid tumors reviewed, breast, ovarian, and prostate cancers have demonstrated efficacy in the combination of PARP inhibition and immunotherapy, predominately in BRCA-mutated tumors. However, initial investigations into wildtype BRCA and gastrointestinal tumors have shown moderate overall response or disease control rates, dependent on the tumor type. In contrast, although a number of clinical trials underway, there is a paucity of published results for the use of the combination in lung or urothelial cancers. Overall this article focuses on the promise of combinatorial PARP inhibition and immunotherapy to improve patient outcomes in solid tumors, summarizing both early results and looking toward ongoing trials.

Dataset Information

Therapeutic Potential of Afatinib in NRG1 Fusion-Driven Solid Tumors: A Case Series.

Background

Patients and methods

Results

Conclusion

Key points

Publications

Therapeutic Potential of Afatinib in NRG1 Fusion-Driven Solid Tumors: A Case Series.

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