Circulating tumour DNA predicts response to anti-PD1 antibodies in metastatic melanoma.

Abstract

BACKGROUND:

Programmed death 1 (PD1) inhibitors are now a foundation of medical management of metastatic melanoma. This study sought to determine whether circulating tumour DNA (ctDNA) provides useful early response and prognostic information.

PATIENTS AND METHODS:

We evaluated the relationship between pre-treatment and early on treatment ctDNA and outcome in melanoma patients treated with PD1 inhibitors alone or in combination with ipilimumab.

RESULTS:

ctDNA was detected in 40/76 patients (53%) at baseline, and correlated with stage, LDH levels, disease volume and ECOG performance. RECIST response was 72% (26/36) in group A (undetectable ctDNA at baseline), 77% (17/22) in group B (elevated ctDNA at baseline but undetectable within 12 weeks of therapy) and 6% (1/18) in group C (elevated ctDNA at baseline and remained elevated during treatment). The median PFS was not reached in groups A and B and was 2.7 months for group C [hazard ratio (HR) 0.09; P < 0.001 for group A versus C, and 0.16; P < 0.001 for group B versus C]. The median OS was not reached for groups A and B and was 9.2 months for group C (HR 0.02; P < 0.001 for group A versus C and 0.14; P < 0.001 for group B versus C). The poor outcome measures associated with group C remained significant in multivariate analysis adjusted for LDH, performance status, tumour stage and disease volume. The predictive value for ctDNA for response was confirmed in a separate validation cohort (n = 29, P < 0.01).

CONCLUSION:

Longitudinal assessment of ctDNA in metastatic melanoma patients receiving treatment with PD1 inhibitors is an accurate predictor of tumour response, PFS and OS. Patients who had a persistently elevated ctDNA on therapy had a poor prognosis, and this may guide combination and sequencing of subsequent therapies.

• Authors: J H Lee, G V Long, S Boyd, S Lo, A M Menzies, V Tembe, A Guminski, V Jakrot, R A Scolyer, G J Mann, R F Kefford, M S Carlino, H Rizos
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 28 Issue 5 Pg. 1130-1136 (May 01 2017) ISSN: 1569-8041 [Electronic] England
• PMID: 28327969 (Publication Type: Journal Article)
• Copyright: © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Antibodies, Anti-Idiotypic
• Biomarkers, Tumor
• Circulating Tumor DNA
• Ipilimumab
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor

Topics

• Aged
• Antibodies, Anti-Idiotypic (administration & dosage, immunology)
• Biomarkers, Tumor (blood)
• Circulating Tumor DNA (blood)
• Disease-Free Survival
• Female
• Humans
• Ipilimumab (administration & dosage)
• Male
• Melanoma (blood, drug therapy, pathology)
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging
• Neoplasms, Second Primary (blood, drug therapy)
• Prognosis
• Programmed Cell Death 1 Receptor (antagonists & inhibitors, immunology)