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External Validation of a Dutch Predictive Nomogram for Complete Response to T-VEC in an Independent American Patient Cohort

  • Melanoma
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Talimogene Laherparepvec (T-VEC) is a modified herpes simplex virus type-1 used as intralesional immunotherapy in stage IIIB-IVM1a melanoma patients. Recently, Stahlie et al. published a predictive model for complete response (CR) to T-VEC. This study was designed to validate this model externally in an independent, American patient cohort.

Methods

In total, 71 stage IIIB-IVM1a melanoma patients treated with T-VEC at Moffitt Cancer Center were included. A second nomogram was built incorporating the same predictive factors: tumor size (diameter of largest metastasis), type of metastases (cutaneous, subcutaneous and nodal), and number of metastases (cutoff: < 20 and > 20). Predictive accuracy was assessed through calculation of overall performance, discriminative ability, and calibration.

Results

The two cohorts were similar in many clinicopathologic factors and only differing in tumor mutational status and use of systemic therapy prior to T-VEC. In the validation cohort, 37 (52%) patients showed CR, 22 (31%) partial response (PR), 2 (5.6%) stable disease (SD), and 10 (15%) progressive disease (PD). Of those who demonstrated a CR, 16 (43%) recurred. Overall performance was good (0.164), and discriminative power resulted in fair discriminative ability (0.827). The calibration curve showed slight underestimation for predicted probabilities > 0.15 and slight overestimation <0.15.

Conclusions

The original model as well as the validation model show comparable and good predictive accuracy. The validation model reinforces the conclusion that for the best response to T-VEC, it should be used early on in the course of the disease, when the tumor burden is cutaneous with smaller diameter and fewer of metastases.

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Author notes

  1. Emma H. A. Stahlie and Michael J. Carr contributed equally to this study.

Authors and Affiliations

  1. Department of Surgical Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek (NKI-AVL), Amsterdam, The Netherlands

    Emma H. A. Stahlie MD & Alexander C. J. van Akkooi MD, PhD

  2. Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA

    Michael J. Carr MD & Jonathan S. Zager MD

Authors
  1. Emma H. A. Stahlie MD
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  2. Michael J. Carr MD
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  3. Jonathan S. Zager MD
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  4. Alexander C. J. van Akkooi MD, PhD
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Corresponding author

Correspondence to Alexander C. J. van Akkooi MD, PhD.

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Disclosures

Jonathan S. Zager reports grants from Amgen, Delcath Systems, Philogen, and Provectus; grants and personal fees from Castle Biosciences and Novartis, and personal fees from Pfizer, Merck, and Sun Pharma. Alexander van Akkooi reports advisory board and consultancy honoraria (all paid to institute and unrelated to current work) from Amgen, Bristol- Myers Squibb, Novartis; 4SC, Merck- Pfizer, MSD- Merck, Sanofi and Sirius medical. The remaining authors made no disclosures.

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Stahlie, E.H.A., Carr, M.J., Zager, J.S. et al. External Validation of a Dutch Predictive Nomogram for Complete Response to T-VEC in an Independent American Patient Cohort. Ann Surg Oncol 29, 1637–1644 (2022). https://doi.org/10.1245/s10434-021-11111-w

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  • DOI: https://doi.org/10.1245/s10434-021-11111-w

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