retratamiento con anti-egfr: ¿debe ser guiado por la ...€¦ · rl foro debate oncología 2019....
Post on 28-Jul-2020
2 Views
Preview:
TRANSCRIPT
Retratamiento con anti-EGFR: ¿debe ser guiado por la biopsia liquida?
Dr. Rafael López LópezOncología Médica Traslacional
Hospital Clínico Universitario e Instituto de Investigación SanitariaSantiago de Compostela
10:48RL Foro debate oncología 2019
Disclosures
Advisory role: Roche, AstraZeneca, Merck, MSD, Bayer, BMS, Novartis, Janssen, Lilly, Pfizer, Leo
Speaker’s fee: Roche, Novartis, Pharmamar
Research support: Roche, Merck
Co-founder and shareholder: Nasasbiotech, S.L., Mtrap Inc
10:48
Retratamiento con anti-EGFR: ¿debe ser guiado por la biopsia liquida?
RL Foro debate oncologia 2019
….Sí…claro
10:48
Anti-EGFR rechallenge strategy
Goldberg et al., ESMO Open 2018. doi:10.1136/ esmoopen-2018-000353
RECHALLENGE: Reintroduction, after an intervening treatment, of the same therapy to which tumour has already proved to be resistant
RL Foro debate oncologia 2019
10:48
How to resolve these problem?
RL Foro debate oncologia 2019
Continously monitoring de cancer cells
10:48
From the practical point of view
RL Foro debate oncologia 2019
1 2-5
1-3 2-7
2-7
2-3
2-5
3-15 1-5
1-7
1 5 (3-15) 1-7
1
14-48 days
7-14 days
1.500€-30.000€ (one)
300€-3.000€(one)
10:48
Clonal evolution of CRC
Siravenga et al., Nature Rev 2017
RL Foro debate oncologia 2019
From the scientific point of view
10:48
Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients
Emergence of RAS mutations at progression to anti-EGFR treatmentBaseline
PD
Vidal et al., Annals of Oncology, 2017
RL Foro debate oncologia 2019
10:48Van Emburgh. Nat Comm 2016
Emergence of mutations of resistance in mCRC patients with anti-EGFR
Dienstmann et al., Ann Oncol , 2016
RL Foro debate oncología 2019
Resistance to anti-EGFR mAbs
10:48
Retreatment with anti-EGFR based therapies in metastatic colorectal cancer:
impact of intervening time interval and prior anti-EGFR response
Liu et al. BMC Cancer 2015;15:713; Goldberg et al., ESMO Open 2018.
RL Foro debate oncologia 2019
10:48RL Foro debate oncologia 2019
10:48
INCLUSION CRITERIAHistologically confirmed diagnosis of metastatic colorectal cancer;Documented WT RAS exons 2, 3 and 4 (KRas and NRas) and WT BRAF V600E;Complete or partial response to frontline chemotherapy including anti-EGFR mAb.Imaging documented progression while on therapy or maintenance regimen including anti-EGFR mAb;RAS-extended mutational load with > 3% fractional abundance, measured on plasma ctDNA at BML (maximum within 2 weeks of last anti EGFR administration);Planned 2nd line chemotherapy of any type with the exclusion of further anti EGFRs (regorafenib is allowed).
Rechallenge With Panitumumab Driven by RAS
Dynamic of Resistance (CHRONOS)
RL Foro debate oncologia 2019
10:48RL Foro debate oncologia 2019
Khan et al., Cancer Discov, 2018
The PROSPECT-C trial
10:48
Longitudinal Liquid Biopsy and Mathematical Modeling of Clonal Evolution Forecast Time to Treatment Failure in the
PROSPECT-C Phase II Colorectal Cancer Clinical Trial
Khan et al., Cancer Discov, 2018
RL Foro debate oncologia 2019
10:48RL Foro debate oncologia 2019
Cremolini C et al. JAMA Oncol. doi:10.1001/jamaoncol.2018.5080
The CRICKET trial (a proof-of-concept study)
A, Hazard ratio, 0.44 (95%CI, 0.18-0.98; P = .03). B, Hazard ratio, 0.58 (95% CI, 0.22-1.52; P = .24).
10:48RL Foro debate oncología 2019
10:48
Take Home Message
• Rechallenge with anti-EGFR provides clinical benefit in molecularlyselected mCRC patients beyond second line.
• ctDNA analyses to determine RAS and other genes status will be a key element to guide rechallenge in CRC patients
• Ongoing clinical trials will solidify the concept of anti-EGFR rechallenge as a routine strategy to optimise the therapy
• Additional biomarkers of response to anti-EGFR agents will ensuredefinition of the optimal patient populations for these strategies
RL Foro debate oncologia 2019
10:48
Future
RL Foro debate oncología 2019
Heitzer et al Nat Rew Genetics 2018 doi.org/10.1038/s41576-018-0071-5
rafael.lopez.lopez@sergas.eswww.oncomet.es
top related