Abstract
Neuroendocrine carcinoma (NEC) of the gallbladder origin is particularly rare, accounting for only 0.38% of primary malignancies of the gallbladder, and standard therapies are limited. The MET gene encodes the tyrosine kinase receptor, c-Met. Pathogenic variants of MET, such as MET exon 14 skipping and MET amplification, result in excessive downstream signaling that promotes tumor progression. A MET inhibitor, capmatinib, blocks signaling of c-Met and has been approved by the Food and Drug Administration for non-small cell lung cancer with MET exon 14 skipping. The effectiveness of capmatinib has been reported in other cancers with MET amplification, but NEC with MET variants has not been reported. Here, we present a case of a 72-year-old woman with NEC of the gallbladder with multiple liver and lymph node metastases, who was resistant to conventional chemotherapy including carboplatin plus etoposide as first-line treatment and irinotecan as second-line treatment, but she responded to capmatinib. After 6 weeks of treatment, CT scan showed a partial response (80% reduction in size), but after 13 weeks, regrowth of liver metastasis was observed. Herein, we report a meaningful efficacy of capmatinib to the patient of NEC of the gallbladder origin with MET amplification.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Explore related subjects
Discover the latest articles and news from researchers in related subjects, suggested using machine learning.Data availability
The datasets used during the current study are available from the corresponding author on reasonable request.
References
Oronsky B et al (2017) Nothing but NET: a review of neuroendocrine tumors and carcinomas. Neoplasia 19(12):991–1002
Tong JH, Yeung SF, Chan AWH et al (2016) MET amplification and exon 14 splice site mutation define unique molecular subgroups of non-small cell lung carcinoma with poor prognosis. Clin Cancer Res 22:3048–3056
Lemmon MA, Schlessinger J (2010) Cell signaling by receptor tyrosine kinases. Cell 141:1117–1134
Schaeper U, Gehring NH, Fuchs KP, Sachs M, Kempkes B, Birchmeier W (2000) Coupling of Gab1 to c-Met, Grb2, and Shp2 mediates biological responses. J Cell Biol 149:1419–1432
Baltschukat S et al (2019) Capmatinib (INC280) is active against models of non-small cell lung cancer and other cancer types with defined mechanisms of MET activation. Clin Cancer Res 25(10):3164–3175
Wolf J, Seto T, Han JY et al (2020) Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer. N Engl J Med 383:944–957
Daniel SL et al (2022) Partial treatment response to capmatinib in MET-amplified metastatic intrahepatic cholangiocarcinoma: case report and review of literature. Cancer Biol Thor 23(1):112–116
Manisha H et al (2021) Neuroendocrine and adrenal tumors, version 2. 2021, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw 19(7):869–868
Awad MM, Oxnard GR, Jackman DM et al (2016) MET exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression. J Clin Oncol 34:721–730
Frampton GM, Ali SM, Rosenzweig M et al (2015) Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov 5(8):850–859
Paik PK, Felip E, Veillon R et al (2020) Tepotinib in non-small-cell lung cancer with MET exon 14 skipping mutations. N Engl J Med 383(10):931–943
Anthony T (2022) Response to capmatinib in a MET fusion-positive cholangiocarcinoma. Oncologist 28(1):80–83
Faivre SJ et al (2021) Activity of tepotinib in hepatocellular carcinoma (HCC) with high-level MET amplification (METamp): preclinical and clinical evidence. J Clin Oncol 39(3_suppl):329
Le X et al (2021) Tepotinib in patients (pts) with advanced non-small cell lung cancer (NSCLC) with MET amplification (METamp). J Clin Oncol 39(15):9021
Park K et al (2019) Tepotinib in NSCLC patients harboring METex14 skipping: cohort A of phase II VISION study. Ann Oncol 30(9_suppl):ix22–ix23
Lee J et al (2019) Tumor genomic profiling guides patients with metastatic gastric cancer to targeted treatment: the VIKTORY umbrella trial. Cancer Discov 9(10):1388–1405
Turke AB, Zejnullahu K, Wu YL et al (2010) Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer Cell 17:77–88
Wu YL, Soo RA, Locatelli G, Stammberger U, Scagliotti G, Park K (2017) Does cMet remain a rational target for therapy in patients with EGFR TKI resistant non-small cell lung cancer? Cancer Treat Rev 61:70–81
Remon J, Morán T, Majem M et al (2014) Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in EGFR-mutant nonsmall cell lung cancer: a new era begins. Cancer Treat Rev 40:93–101
Lin JJ, Johnson T, Lennerz JK et al (2020) Resistance to lorlatinib in ROS1 fusion-positive non-small cell lung cancer. J Clin Oncol 38(suppl 15):9611
Awad MM, Liu S, Rybkin II et al (2021) Acquired resistance to KRAS G12C inhibition in cancer. N Engl J Med 384(25):2382–2393
Dagogo-Jack I, Yoda S, Lennerz JK et al (2020) MET alterations are a recurring and actionable resistance mechanism in ALK-positive lung cancer. Clin Cancer Res 26:2535–2545
Daniel SL, Marni BT et al (2022) Partial treatment response to capmatinib in MET-amplified metastatic intrahepatic cholangiocarcinoma: case report & review of literature. Cancer Biol Ther 23(1):112–116
Anthony T, Clotilde D, Valerie G et al (2023) Response to capmatinib in a MET fusion-positive cholangiocarcinoma. Oncologist 28:80–83
Gao J et al (2013) Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 6(269):l1
Acknowledgements
The authors would like to thank the patients for their kind cooperation and Enago (www.enago.jp) for the English Language review.
Funding
This research was supported by a Grant-in-Aid for Scientific Research C (17K08413) from the Japan Society for the Promotion of Science and by the Japan Agency for Medical Research and Development, AMED, under Grant number 17kk0305006h0001.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Masashi Kanai own stocks in Therabiopharma and received honoraria from Chugai Pharmaceutical Co., Ltd. Taro Funakoshi belongs to an endowed chair sponsored partly by Yakult Honsha Co., Ltd. and Chugai Pharmaceutical Co., Ltd. Manabu Muto received research funding and honoraria from Chugai Pharmaceutical Co., Ltd. All remaining authors have no conflict of interest to declare.
Ethics approval
This report was supported by research on “The prospective trial of patient-proposed healthcare services with multiple targeted agent based on the result of gene profiling by multigene panel test (NCCH1901/jRCTs031190104)” of the Clinical Research Review Committee, National Cancer Center Hospital, under Grant number CRB3180008.
Consent for publication
We obtained consent of the patient for participating in the NCCH1901 study and publication related to this study. A copy of the consent form with the patient's signature can be submitted.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Yamamura, S., Kanai, M., Takeuchi, Y. et al. Response to capmatinib in a patient with neuroendocrine carcinoma of the gallbladder origin harboring MET amplification. Int Canc Conf J 13, 83–87 (2024). https://doi.org/10.1007/s13691-023-00643-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13691-023-00643-5