Abstract 2046
Background
Translating results from randomized trials to individual patients is challenging since treatment effects may vary due to heterogeneous prognostic characteristics. We aimed to demonstrate model development for individualized treatment effect predictions in cancer patients. We used data from two randomized trials that investigated combination (ComC) versus sequential chemotherapy (SeqC) in unresectable metastatic colorectal cancer (mCRC) patients.
Methods
We used data from 803 patients included in CAIRO for prediction model development and internal validation, and data from 1423 patients included in FOCUS for external validation. A Weibull model with prespecified patient and tumour characteristics was developed for a prediction of gain in median overall survival by upfront ComC versus SeqC. Decision curve analysis with net benefit was used. A nomogram was built for estimating the probability of receiving second-line treatment after first-line monochemotherapy.
Results
Median predicted gain in overall survival for ComC versus SeqC was 2.3 months (IQR -1.1-3.7 months). A gain in favour of SeqC was found in 231 patients (29%) and a gain of > 3 months for ComC in 294 patients (37%). Patients with benefit from SeqC had metachronous metastatic disease and a left-sided primary tumour. Decision curve analyses showed improvement in net benefit for treating all patients according to prediction-based treatment compared to treating all patients with ComC. Multiple characteristics were identified as prognostic variables that identify patients at risk of never receiving second-line treatment if treated with initial monochemotherapy. External validation showed good calibration with moderate discrimination in both models (C-index 0.66 and 0.65, respectively).
Conclusions
We successfully developed individualized prediction models including prognostic characteristics derived from randomized trials to estimate treatment effects in mCRC patients. In times where the heterogeneity of CRC becomes increasingly evident, such tools are an important step towards personalized treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Koopman: Research grant / Funding (institution): Dutch Colorectal Cancer Group; Advisory / Consultancy: Servier. J.J. Kwakman: Honoraria (self), Research grant / Funding (institution): Nordic Pharma; Advisory / Consultancy, Research grant / Funding (institution): Servier. C.J.A. Punt: Research grant / Funding (institution): Dutch Colorectal Cancer Group; Advisory / Consultancy: Servier. All other authors have declared no conflicts of interest.
Resources from the same session
2104 - Clinical implications of regorafenib-induced hypothyroidism in metastatic colorectal cancer refractory to standard therapies: A prospective evaluation
Presenter: Jwa Hoon Kim
Session: Poster Display session 2
Resources:
Abstract
2143 - Clinical impact of BRAF V600E mutations in patients (pts) with resectable solitary colorectal liver metastases (CRLM)
Presenter: Shin Kobayashi
Session: Poster Display session 2
Resources:
Abstract
3136 - Trifluridine/tipiracil in metastatic colorectal cancer: an updated multicentre real-world analysis on efficacy, safety and predictive factors.
Presenter: Chara Stavraka
Session: Poster Display session 2
Resources:
Abstract
4234 - Correlation between p53 expression and clinical outcome in RAS/BRAF wild type metastatic colorectal cancer patients receiving later-line irinotecan-cetuximab
Presenter: Eleonora Lai
Session: Poster Display session 2
Resources:
Abstract
4287 - Safety and effectiveness of aflibercept + FOLFIRI for the treatment of patients with metastatic colorectal cancer (mCRC): OZONE secondary analyses
Presenter: Ian Chau
Session: Poster Display session 2
Resources:
Abstract
1820 - A Phase Ib study of the safety and efficacy of atezolizumab (atezo) + bevacizumab (bev) + cobimetinib (cobi) in patients (pts) with metastatic colorectal cancer (mCRC)
Presenter: Johanna Bendell
Session: Poster Display session 2
Resources:
Abstract
5644 - Development and validation of a metastasis-associated immune prognostic model for concurrent metastatic colorectal cancer
Presenter: Zhiwen Luo
Session: Poster Display session 2
Resources:
Abstract
5697 - Prognostic role of blood cell count-based immuno-inflammatory parameters in the Valentino trial
Presenter: Giovanni Fuca
Session: Poster Display session 2
Resources:
Abstract
4704 - Evaluation of safety, immunogenicity and preliminary efficacy of PolyPEPI1018 vaccine in subjects with metastatic colorectal cancer (mCRC) with a predictive biomarker
Presenter: Joleen Hubbard
Session: Poster Display session 2
Resources:
Abstract
3266 - Morphology of tumor-associated macrophages dictates the prognosis of patients with colorectal liver metastases.
Presenter: Matteo Donadon
Session: Poster Display session 2
Resources:
Abstract