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Multicenter phase II study of the AKT inhibitor MK-2206 in recurrent or metastatic nasopharyngeal carcinoma from patients in the mayo phase II consortium and the cancer therapeutics research group (MC1079)

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Summary

Background This study investigated the activity of MK-2206, an AKT inhibitor, in metastatic or recurrent nasopharyngeal carcinoma (NPC). Method Oral MK-2206 at a dose of 200 mg was administered on days 1, 8, 15 and 22 of a 28-day cycle until progression. Plasma EBV DNA clearance during the first month of treatment was measured, and archived tumors were analyzed for the expression of AKT and PIK3CA mutation and PIK3CA amplification. The dual primary endpoint was objective response rate and 6-month progression-free survival (PFS) rate. Results 21 patients were enrolled and one patient achieved a partial response (5 %) and 11 had stable disease (52 %), with a median PFS of 3.5 months (95 % confidence interval, CI: 0.9–7.3). The 6-month PFS rate was 43 % (95 % CI: 22–66 %) and the median OS was 10 months (95 % CI: 5.9 months–not reached). Seven patients (33 %) experienced grade 3 toxicities which could be related to MK-2206. Macular-papular rash was the most common (n = 6), followed by hyperglycemia (n = 2) and fatigue (n = 1). In the 12 tumor samples analyzed, PIK3CA amplification was detected in one patient’s primary NPC, who had SD lasting over 12 months. Patients with decreasing EBV DNA values over time were more likely to be alive and progression-free for at least 6 months than those without a decrease (p = 0.001). Conclusion The study was terminated due to the limited activity observed in this heavily pre-treated group of patients. Further studies are needed to elucidate the optimal way of selecting patients for AKT inhibitors.

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Acknowledgments

This study was supported by the National Cancer Institute/Cancer Therapy Evaluation Program (Protocol #8761), Mayo Clinic Phase II consortium grant (N01-CM62205, PI, Dr C. Erlichman). The genomic analysis was supported by the Theme-Based Research Scheme (T12-401/13-R), Research Grants Council, Hong Kong SAR. This work was presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, MA, October 2013, abstract B273. NCT01370070.

Disclosure

G. de Lima Lopes: research grants, honoraria, consultancy with Merck Sharpe and Dohme.

K.C. Chan: filed patents on technologies related to molecular diagnostics for cancers.

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Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Sir Y.K. Pao Centre for Cancer, Department of Clinical Oncology, Chinese University of Hong Kong, Shatin, Hong Kong SAR

    B. B. Y. Ma, E. P. Hui, L. Li, H. Loong & A. T. C. Chan

  2. National University Hospital, Cancer Science Institute of Singapore, Singapore, Singapore

    B. C. Goh

  3. National Cancer Center Singapore, Investigational Medicine Unit, Singhealth, Singapore, Singapore

    W. T. Lim & E. H. Tan

  4. Johns Hopkins Singapore International Medical Centre, Singapore, Singapore

    G. de Lima Lopes

  5. Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Shatin, Hong Kong SAR

    K. W. Lo

  6. Mayo Clinic, Rochester, MN, USA

    N. R. Foster & C. Erlichman

  7. Department of Clinical Oncology, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR

    B. B. Y. Ma, M. K. M. Kam & S. F. Leung

  8. Department of Radiology, Chinese University of Hong Kong, Shatin, Hong Kong SAR

    A. D. King

  9. Department of Chemical Pathology, Chinese University of Hong Kong, Shatin, Hong Kong SAR

    K. C. Chan

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  1. B. B. Y. Ma
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Ma, B.B.Y., Goh, B.C., Lim, W.T. et al. Multicenter phase II study of the AKT inhibitor MK-2206 in recurrent or metastatic nasopharyngeal carcinoma from patients in the mayo phase II consortium and the cancer therapeutics research group (MC1079). Invest New Drugs 33, 985–991 (2015). https://doi.org/10.1007/s10637-015-0264-0

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  • DOI: https://doi.org/10.1007/s10637-015-0264-0

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