Circulating tumor DNA as a biomarker in metastatic melanoma patients treated with anti-PD1 antibodies

J. Lee, S. Boyd, V. Tembe, A. Menzies, G. Long, A. Guminski, R. Kefford, M. Carlino, H. Rizos

Research output: Contribution to journal › Meeting abstract › Research

Abstract

Background: Changes in circulating tumor DNA (ctDNA) levels correlate with response to MAPK inhibitors in patients with advanced melanoma, but the utility of ctDNA as a biomarker for immunotherapy remains unknown. In this study, ctDNA was monitored in melanoma patients treated with PD1 inhibitor alone or in combination with a CTLA4 inhibitor. Methods: Mutation-specific droplet digital PCR was used to measure ctDNA in patients with a known tumor-associated mutation. ctDNA levels were determined prior to therapy and during treatment, and correlated to RECIST 1.1 response at week 12. Results: In 85 patients with available week 12 response data, undetectable ctDNA at baseline (n = 40) was associated with a higher response rate (Table 1, P <0.05), and higher ORR was observed when brain progression was excluded (Table 1, P <0.01). ctDNA levels were monitored early during therapy in 80 patients (up to week 12, and in 75 patients ctDNA was measured prior to week 6). RECIST responses were more common in those with undetectable ctDNA early on treatment (Table 1, P <0.01), with ORR of 90% observed when intracranial progression only was excluded (Table 1, P <0.01). Conclusions: This is the single largest study to date demonstrating the utility of ctDNA in monitoring response to anti-PD1 therapy in melanoma. We note that ctDNA levels are not an accurate predictor of response in patients with predominant brain metastases. We confirm that undetectable ctDNA early during treatment is a strong indicator of response to anti-PD1 therapy. [table included in full text]
LanguageEnglish
Pages48-49
Number of pages2
JournalAsia-Pacific journal of clinical oncology : special issue : implementation + innovation in immunotherapy
Publication statusPublished - 2016
EventAnnual Scientific Meeting of the Medical Oncology Group of Australia (2016) -
Duration: 3 Aug 2016 → 5 Aug 2016

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Anti-Idiotypic Antibodies
Melanoma
Biomarkers
DNA
Neoplasms
Therapeutics
Mutation
Brain
Secondary Prevention
Immunotherapy
Neoplasm Metastasis
Polymerase Chain Reaction

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Lee, J. ; Boyd, S. ; Tembe, V. ; Menzies, A. ; Long, G. ; Guminski, A. ; Kefford, R. ; Carlino, M. ; Rizos, H. / Circulating tumor DNA as a biomarker in metastatic melanoma patients treated with anti-PD1 antibodies. In: Asia-Pacific journal of clinical oncology : special issue : implementation + innovation in immunotherapy. 2016 ; pp. 48-49.
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title = "Circulating tumor DNA as a biomarker in metastatic melanoma patients treated with anti-PD1 antibodies",
abstract = "Background: Changes in circulating tumor DNA (ctDNA) levels correlate with response to MAPK inhibitors in patients with advanced melanoma, but the utility of ctDNA as a biomarker for immunotherapy remains unknown. In this study, ctDNA was monitored in melanoma patients treated with PD1 inhibitor alone or in combination with a CTLA4 inhibitor. Methods: Mutation-specific droplet digital PCR was used to measure ctDNA in patients with a known tumor-associated mutation. ctDNA levels were determined prior to therapy and during treatment, and correlated to RECIST 1.1 response at week 12. Results: In 85 patients with available week 12 response data, undetectable ctDNA at baseline (n = 40) was associated with a higher response rate (Table 1, P <0.05), and higher ORR was observed when brain progression was excluded (Table 1, P <0.01). ctDNA levels were monitored early during therapy in 80 patients (up to week 12, and in 75 patients ctDNA was measured prior to week 6). RECIST responses were more common in those with undetectable ctDNA early on treatment (Table 1, P <0.01), with ORR of 90{\%} observed when intracranial progression only was excluded (Table 1, P <0.01). Conclusions: This is the single largest study to date demonstrating the utility of ctDNA in monitoring response to anti-PD1 therapy in melanoma. We note that ctDNA levels are not an accurate predictor of response in patients with predominant brain metastases. We confirm that undetectable ctDNA early during treatment is a strong indicator of response to anti-PD1 therapy. [table included in full text]",
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Lee, J, Boyd, S, Tembe, V, Menzies, A, Long, G, Guminski, A, Kefford, R, Carlino, M & Rizos, H 2016, 'Circulating tumor DNA as a biomarker in metastatic melanoma patients treated with anti-PD1 antibodies', Asia-Pacific journal of clinical oncology : special issue : implementation + innovation in immunotherapy, pp. 48-49.

Circulating tumor DNA as a biomarker in metastatic melanoma patients treated with anti-PD1 antibodies. / Lee, J.; Boyd, S.; Tembe, V.; Menzies, A.; Long, G.; Guminski, A.; Kefford, R.; Carlino, M.; Rizos, H.

In: Asia-Pacific journal of clinical oncology : special issue : implementation + innovation in immunotherapy, 2016, p. 48-49.

Research output: Contribution to journal › Meeting abstract › Research

TY - JOUR

T1 - Circulating tumor DNA as a biomarker in metastatic melanoma patients treated with anti-PD1 antibodies

AU - Lee, J.

AU - Boyd, S.

AU - Tembe, V.

AU - Menzies, A.

AU - Long, G.

AU - Guminski, A.

AU - Kefford, R.

AU - Carlino, M.

AU - Rizos, H.

PY - 2016

Y1 - 2016

N2 - Background: Changes in circulating tumor DNA (ctDNA) levels correlate with response to MAPK inhibitors in patients with advanced melanoma, but the utility of ctDNA as a biomarker for immunotherapy remains unknown. In this study, ctDNA was monitored in melanoma patients treated with PD1 inhibitor alone or in combination with a CTLA4 inhibitor. Methods: Mutation-specific droplet digital PCR was used to measure ctDNA in patients with a known tumor-associated mutation. ctDNA levels were determined prior to therapy and during treatment, and correlated to RECIST 1.1 response at week 12. Results: In 85 patients with available week 12 response data, undetectable ctDNA at baseline (n = 40) was associated with a higher response rate (Table 1, P <0.05), and higher ORR was observed when brain progression was excluded (Table 1, P <0.01). ctDNA levels were monitored early during therapy in 80 patients (up to week 12, and in 75 patients ctDNA was measured prior to week 6). RECIST responses were more common in those with undetectable ctDNA early on treatment (Table 1, P <0.01), with ORR of 90% observed when intracranial progression only was excluded (Table 1, P <0.01). Conclusions: This is the single largest study to date demonstrating the utility of ctDNA in monitoring response to anti-PD1 therapy in melanoma. We note that ctDNA levels are not an accurate predictor of response in patients with predominant brain metastases. We confirm that undetectable ctDNA early during treatment is a strong indicator of response to anti-PD1 therapy. [table included in full text]

AB - Background: Changes in circulating tumor DNA (ctDNA) levels correlate with response to MAPK inhibitors in patients with advanced melanoma, but the utility of ctDNA as a biomarker for immunotherapy remains unknown. In this study, ctDNA was monitored in melanoma patients treated with PD1 inhibitor alone or in combination with a CTLA4 inhibitor. Methods: Mutation-specific droplet digital PCR was used to measure ctDNA in patients with a known tumor-associated mutation. ctDNA levels were determined prior to therapy and during treatment, and correlated to RECIST 1.1 response at week 12. Results: In 85 patients with available week 12 response data, undetectable ctDNA at baseline (n = 40) was associated with a higher response rate (Table 1, P <0.05), and higher ORR was observed when brain progression was excluded (Table 1, P <0.01). ctDNA levels were monitored early during therapy in 80 patients (up to week 12, and in 75 patients ctDNA was measured prior to week 6). RECIST responses were more common in those with undetectable ctDNA early on treatment (Table 1, P <0.01), with ORR of 90% observed when intracranial progression only was excluded (Table 1, P <0.01). Conclusions: This is the single largest study to date demonstrating the utility of ctDNA in monitoring response to anti-PD1 therapy in melanoma. We note that ctDNA levels are not an accurate predictor of response in patients with predominant brain metastases. We confirm that undetectable ctDNA early during treatment is a strong indicator of response to anti-PD1 therapy. [table included in full text]

UR - https://doi.org/10.1111/ajco.12542

M3 - Meeting abstract

SP - 48

EP - 49

JO - Asia-Pacific journal of clinical oncology : special issue : implementation + innovation in immunotherapy

T2 - Asia-Pacific journal of clinical oncology : special issue : implementation + innovation in immunotherapy

JF - Asia-Pacific journal of clinical oncology : special issue : implementation + innovation in immunotherapy

SN - 1743-7555

ER -

Lee J, Boyd S, Tembe V, Menzies A, Long G, Guminski A et al. Circulating tumor DNA as a biomarker in metastatic melanoma patients treated with anti-PD1 antibodies. Asia-Pacific journal of clinical oncology : special issue : implementation + innovation in immunotherapy. 2016;48-49.

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