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Clinical Benefit from Tyrosine Kinase Inhibitors in Metastatic Merkel Cell Carcinoma: A Case Series of 5 Patients.

ABSTRACT: BACKGROUND Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin cancer. The estimated 5-year survival of patients with metastatic disease is approximately 14%. Cytotoxic chemotherapy is associated with a modest median progression-free survival (PFS) of only 3 months. In recent studies, immunotherapy with anti-PD-1/anti-PD-L1 antibodies has demonstrated a high response rate in immunocompetent patients (>50% in chemotherapy-naïve patients) and responses are typically durable. However, approximately 50% of immunocompetent patients do not respond to immunotherapy. In addition, immunosuppressed patients have limited therapeutic options. Hence, there is a significant unmet need for effective treatments in these subpopulations. CASE REPORT We describe 5 patients (out of 24 total) with metastatic MCC who were treated with a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI), either pazopanib (n=4) or cabozantinib (n=1), with clinical benefit. One patient had a complete response to pazopanib after 3 months of therapy. Four patients had stabilization of disease that lasted from 5 months to 3.5 years. In an immunosuppressed patient with psoriatic arthritis, stabilization of MCC was also associated with improvement in his arthritis that allowed cessation of immunosuppression. Patients did not develop any unusual toxicities from VEGFR-TKIs. CONCLUSIONS Treatment with VEGFR-TKIs demonstrated clinical benefit in this selected small group of patients with metastatic MCC. Prospective investigation of VEGFR-TKIs is warranted in this population, especially in patients with disease refractory to immunotherapy.

SUBMITTER: Tarabadkar ES

PROVIDER: S-EPMC5952731 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Clinical Benefit from Tyrosine Kinase Inhibitors in Metastatic Merkel Cell Carcinoma: A Case Series of 5 Patients.

Tarabadkar Erica S ES Thomas Hannah H Blom Astrid A Parvathaneni Upendra U Olencki Thomas T Nghiem Paul P Bhatia Shailender S

The American journal of case reports 20180430

BACKGROUND Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin cancer. The estimated 5-year survival of patients with metastatic disease is approximately 14%. Cytotoxic chemotherapy is associated with a modest median progression-free survival (PFS) of only 3 months. In recent studies, immunotherapy with anti-PD-1/anti-PD-L1 antibodies has demonstrated a high response rate in immunocompetent patients (>50% in chemotherapy-naïve patients) and responses are typically durable. H ...[more]

PMID: 29706615

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Project description:The optimal management of advanced non-small cell lung cancer (NSCLC) with noncanonical epidermal growth factor receptor (EGFR) mutations (i.e., exon 19 deletion and exon 21 L858R) is constrained by the heterogeneous behavior of individual uncommon mutations and limited prospective clinical data in this setting. Despite encouraging results with osimertinib from a recently published phase II trial from South Korea, afatinib remains the only currently approved drug for patients with tumors harboring uncommon EGFR mutations (i.e., S768I, L861Q, and/or G719X). When used at the standard dose of 40 mg daily, afatinib is associated with significant rates of treatment-related adverse events, leading to frequent dose reductions and treatment discontinuations. We report a case of a woman with advanced NSCLC harboring EGFR-G719A mutation treated with afatinib (at an off-label pulse dose strategy that merits further evaluation in prospective studies) with sustained partial response for 20 months with manageable expected toxicities. Subsequent disease progression was mediated by off-target pan-EGFR inhibitor (including osimertinib)-resistant KRAS mutation and not by acquisition of EGFR-T790M. We further present the current state of evidence in the literature behind use of first-, second-, and third-generation tyrosine kinase inhibitors and summarize the evolving spectrum of activity ascribed to osimertinib (and newer EGFR inhibitors with a more favorable therapeutic window and intracranial penetration) in this population of patients with advanced NSCLC and uncommon EGFR mutations. KEY POINTS: Uncommon EGFR mutations characterize a heterogeneous group of patients with advanced non-small cell lung cancer (NSCLC). Afatinib is the only currently U.S. Food and Drug Administration-approved drug for management of advanced NSCLC with uncommon EGFR mutations (S768I, L861Q, and/or G719X). Afatinib treatment at 40 mg daily is associated with high rates of adverse events and dose reductions; alternative strategies including pulse intermittent dosing should be evaluated prospectively. Osimertinib (with favorable safety profile and intracranial penetration) has shown promising results in this population in a phase II trial from South Korea; additional trials are ongoing.

Dataset Information

Clinical Benefit from Tyrosine Kinase Inhibitors in Metastatic Merkel Cell Carcinoma: A Case Series of 5 Patients.

Publications

Clinical Benefit from Tyrosine Kinase Inhibitors in Metastatic Merkel Cell Carcinoma: A Case Series of 5 Patients.

Similar Datasets

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