Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Sequential RAS mutation testing in cfDNA in RAS wild type (wt) metastatic colorectal cancer (mCRC) patients (pt) treated with panitumumab (P) and chemotherapy (CT) in first line (1L). PERSEIDA study

Date

29 Sep 2019

Session

Poster Discussion – Gastrointestinal tumours, colorectal

Presenters

Manuel Valladares-Ayerbes

Citation

Annals of Oncology (2019) 30 (suppl_5): v198-v252. 10.1093/annonc/mdz246

Authors

M. Valladares-Ayerbes1, P. García-Alfonso2, J. Muñoz Luengo3, P. Pimentel Cáceres4, J.M. Viéitez5, J.J. Cruz-Hernández6, M. Llanos7, C. Garcia Girón8, L. Cirera9, A. Lloansí Vila10

Author affiliations

  • 1 Medical Oncology Departament, University Hospital Reina Sofia, 14004 - Cordoba/ES
  • 2 Medical Oncology, Hospital General Universitario Gregorio Marañón, Madrid/ES
  • 3 Medical Oncology, Hospital San Pedro de Alcántara, Cáceres/ES
  • 4 Medical Oncology, Hospital General Universitario Santa Lucia, Cartagena/ES
  • 5 Medical Oncology, MD Anderson, Madrid/ES
  • 6 Medical Oncology, Hospital Universitario de Salamanca, Salamanca/ES
  • 7 Medical Oncology, Hospital Universitario de Canarias, Santa Cruz de Tenerife/ES
  • 8 Medical Oncology, Hospital Universitario de Burgos, Burgos/ES
  • 9 Medical Oncology, Hospital Universitario Mutua Terrassa, Terrassa/ES
  • 10 Medical Advisor, Amgen, Barcelona/ES
More

Resources

Background

Genotyping on cfDNA offers potential advantages in clinical practice for pt selection and serial monitoring of treatment (Tx) efficacy. Clinical relevance of sequential RASmut in cfDNA at different time points during 1L of pt with RASwt solid biopsies (SB) was evaluated.

Methods

Prospective, multi-center study in mCRC pt with RASwt according to SB and treated following standard practice. Liquid biopsies (LB) were collected before starting 1L, at 20 (± 2) weeks (w) and at disease progression (PD). Beaming PCR was used for cfDNA analysis; 3 mutant allele fraction (MAF) cutoffs were considered: 1%, 0.1% & 0.02%.

Results

Median progression-free survival (PFS) was 11.7 months (m) (9.9-13.0) (n = 102). There were no differences in the overall response rate (ORR) according to baseline LB at any cut off, being at MAF 0.02%: 78.7% (68.2- 87.1) in RASwt pt (n = 80) vs 61.5% (31.6 - 86.1) in RASmut pt (n = 13) (OR: 2.32; p = 0.180). MAF was not correlated with total cfDNA levels (p = 0.957). The % of mut cfDNA pt varied along time, with the smallest % at 20 w (Table). There were no emergent mutations at 20 w. Ten pt wt according to baseline LB presented mutations at PD. ORR was 76.9% (63.2 - 87.5) in pt always wt (n = 52) vs 76.2% (52.8 - 91.8) in pt with mut cfDNA at any time point (n = 21) (p = 1.0). There were also no differences in PFS between these 2 groups of pt: 13.0 m (10.9 - 15.4) vs 11.4 m (7.1 – 13.7) at MAF 0.02% (p = 0.095).Table:

531PD

MAF≥1%MAF≥0.1%MAF≥0.02%
Baseline3 (2.9%) n = 1026 (5.9%) n = 10214 (13.7%) n = 102
PFS RASwt: 11.7 m (9.9-13.0) RASmt: NR (5.9-NR) (p = 0.689)PFS RASwt: 11.7 m (9.9-13.1) RASmt: 7.8 m (5.9-NR) (p = 0.662)PFS RASwt: 11.7 m (9.9-13.1) RASmt: 11.4 m (5.9-18.5) (p = 0.495)
20 ± 2 weeks0 (0%) n = 763 (4.0%) n = 764 (5.3%) n = 76
PD1 (2.0%) n = 499 (18.4%) n = 4912 (24.5%) n = 49

Proportions of mutated patients based on the number of samples analysed at each time point and progression-free survival (PFS) according to the baseline plasma sample PD Progression of the disease; MAF: Mutant Allele Fraction; NR: not reached

Conclusions

RAS mutational status assessed in cfDNA before starting 1L or sequentially during P+CT Tx in pt with RASwt SB was not a significant predictor of PFS and ORR in none of the cutoffs considered, although in RASmut pt clinical results tended to increase as MAF decreased. The highest proportion of mutated pt was observed at PD, which may be linked to the emergence of resistance. Mutated cfDNA by itself did not predict a lack of clinical benefit to CT and P in our study.

Clinical trial identification

Editorial acknowledgement

Marta Muñoz-Tudurí (TFS, S.L.).

Legal entity responsible for the study

Amgen S.A.

Funding

Amgen S.A.

Disclosure

M. Valladares-Ayerbes: Honoraria (self): Amgen, Merck, Roche, Servier, Bayer, Bristol-Myers; Advisory / Consultancy: Merck, Sanofi, Amgen; Speaker Bureau / Expert testimony: Roche, Servier, Bayer; Research grant / Funding (self): Roche; Travel / Accommodation / Expenses: Merck, Servier, Amgen, Roche. J.M. Viéitez: Travel / Accommodation / Expenses, attendance at conferences: Amgen, Roche, Servier; Research grant / Funding (self): Roche, Amgen. J.J. Cruz-Hernández: Honoraria (self): Amgen, AstraZeneca, Bristol-Myers Squibb, Novartis, Pfizer, Roche Farma; Advisory / Consultancy, Advisory Board: Bristol-Myers Squibb, Merck, MSD, Roche Farma, Pfizer, Janssen Cilag; Advisory / Consultancy, Consulting: Roche Farma. M. Llanos: Advisory / Consultancy, collaboration in lectures: Servier, Roche, Ipsen, Merck, Bristol, Sanofi, Eisai; Advisory / Consultancy: Amgen. A. Lloansí Vila: Shareholder / Stockholder / Stock options, employee and stakeholder of Amgen S.A: Amgen. All other authors have declared no conflicts of interest.

Resources from the same session

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings