Stopping targeted therapy for complete responders in advanced BRAF mutant melanoma

Authors

Lydia Warburton, Edith Cowan UniversityFollow
Tarek M. Meniawy, Edith Cowan UniversityFollow
Leslie Calapre, Edith Cowan UniversityFollow
Michelle Pereira, Edith Cowan UniversityFollow
Ashleigh McEvoy, Edith Cowan UniversityFollow
Mel Ziman, Edith Cowan UniversityFollow
Elin Gray, Edith Cowan UniversityFollow
Michael Millward

Author Identifier

Lydia Warburton

https://orcid.org/0000-0001-9417-1596

Tarek Meniawy

https://orcid.org/0000-0002-1457-6137

Leslie Calapre

https://orcid.org/0000-0001-7595-6523

Michelle Pereira

https://orcid.org/0000-0002-3159-6543

Melanie Ziman

https://orcid.org/0000-0001-7527-3538

Elin Gray

https://orcid.org/0000-0002-8613-3570

Document Type

Journal Article

Publication Title

Scientific Reports

Publisher

Springer Nature

School

School of Medical and Health Sciences

RAS ID

32391

Funders

Edith Cowan University - Open Access Support Scheme 2020

National Health and Medical Research Council of Australia

Grant Number

NHMRC Number : 1117911

Grant Link

http://purl.org/au-research/grants/nhmrc/1117911

Comments

Warburton, L., Meniawy, T. M., Calapre, L., Pereira, M., McEvoy, A., Ziman, M., ... & Millward, M. (2020). Stopping targeted therapy for complete responders in advanced BRAF mutant melanoma. Scientific Reports, 10(1), article 18878. https://doi.org/10.1038/s41598-020-75837-5

Abstract

BRAF inhibitors revolutionised the management of melanoma patients and although resistance occurs, there is a subgroup of patients who maintain durable disease control. For those cases with durable complete response (CR) it is not clear whether it is safe to cease therapy. Here we identified 13 patients treated with BRAF +/− MEK inhibitors, who cease therapy after prolonged CR (median = 34 months, range 20–74). Recurrence was observed in 3/13 (23%) patients. In the remaining 10 patients with sustained CR off therapy, the median follow up after discontinuation was 19 months (range 8–36). We retrospectively measured ctDNA levels using droplet digital PCR (ddPCR) in longitudinal plasma samples. CtDNA levels were undetectable in 11/13 cases after cessation and remained undetectable in patients in CR (10/13). CtDNA eventually became detectable in 2/3 cases with disease recurrence, but remained undetectable in 1 patient with brain only progression. Our study suggests that consideration could be given to ceasing targeted therapy in the context of prolonged treatment, durable response and no evidence of residual disease as measured by ctDNA.

DOI

10.1038/s41598-020-75837-5

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.