Abstract 3426
Background
Benefit of CT beyond standard 1st-line (L1) gemcitabine plus cisplatin (GEMCIS) or oxaliplatin (GEMOX) in aBTC is unclear. Our aim was to identify and validate prognostic factors for L2OS in aBTC to guide patient selection for 2nd line (L2) CT.
Methods
All consecutive patients with aBTC receiving L2 CT after GEMCIS/GEMOX L1 between 2003-2016 in 28 French centers were included. The association of clinico-biological data with L2OS was investigated in univariate and multivariate Cox analyses. A simple score was derived from the multivariate model. The model and score were validated in 3 external cohorts with similar inclusion criteria (Italy, France, UK).
Results
The development cohort included 405 patients treated with L1 GEMOX (91%) or GEMCIS. 55% were men; median age was 64 years. 27% had prior surgical resection; 95% had metastatic disease. Performance status (PS) was 0/1/2 in 18%/52%/30%. Of the 251 patients with available CA19.9 at the beginning of L2, 35% had a CA19.9 ≥ 400 IU/L. Among 22 clinical parameters, 8 were associated with L2OS in univariate analysis. In multivariate analysis, 4 were independent prognostic factors: PS, reason for L1 stopping, prior surgery, peritoneal carcinomatosis (PC) (Table). Type of L2 CT regimen was not associated with L2OS. The clinical model had a C-index of 0.659, a good calibration and was validated in the 3 external cohorts (Table). Analysis of patients with complete data for the 4 clinical factors and CA19.9 (multiple imputations for missing data) showed that CA19.9 was independently associated with L2OS. A score was derived from this model.Table: 765P
Multivariate Cox Model for L2OS (HR, P-value)
| AGEO (N = 405) | ITALY (N = 288) | France (N = 70) | UK (N = 24) | |||||
|---|---|---|---|---|---|---|---|---|
| Prior surgery | ||||||||
| Yes No | 1 1.3 | 0.031 | 1 1.4 | 0.013 | 1 1.8 | 0.16 | 1 4.8 | 0.045 |
| Reason for L1 stopping | ||||||||
| Toxicity/ Other Progression | 1 1.5 | <0.001 | 1 1.8 | <0.001 | 1 3.0 | 0.0063 | 1 31.9 | <0.001 |
| PS | ||||||||
| 0 1 2 | 1 1.5 3.0 | <0.001 | 1 1.2 2.1 | 0.001 | 1 2.0 6.7 | <0.001 | 1 7.4 20.4 | 0.011 |
| PC | ||||||||
| No Yes | 1 1.3 | 0.018 | 1 1.4 | 0.019 | 1 1.0 | 1.0 | 1 15.3 | 0.001 |
Conclusions
We validated L2OS prognostic factors previously reported and identified PC as a new pejorative one in 800+ patients. Our model and score will be useful for guiding therapeutic decisions and stratifying randomization in future clinical trials.
Clinical trial identification
Legal entity responsible for the study
AGEO (Association des GastroEntérologues Oncologues) academic group.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
C. Neuzillet: Research funding (outside the study): Celgene; Clinical trial PI: AstraZeneca. A. Casadei Gardini: Consulting, Advisory role: Eisai; Speakers\' bureau: Bayer. B.J.-C. Rousseau: Advisory board: Bayer. M. Scartozzi: Consulting Advisory role, Speakers\' bureau: Bayer, Amgen, Merck, Sanofi; Research funding : Bayer, Msd, Bms, Sanofi. A. Lievre: Consulting, Advisory role: Merck, Amgen, Bayer, Ipsen, Shire; Speakers\' bureau: Merck, Roche, Amgen, Bayer, Ipsen, Novartis, BMS. All other authors have declared no conflicts of interest.
Resources from the same session
5720 - Evaluation of stemness and proliferation of human breast cancer stem cells (ALDH+) supplemented with heat-activated TGF-beta1 in the secretomes of stem cells from human exfoliated deciduous teeth (SHED)
Presenter: Septelia Wanandi
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
4844 - Estrogen-related receptor _ as a potential molecular target for endometrial cancer therapy
Presenter: TETSUYA KOKABU
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1200 - Good tolerability and limited target-specific tissue distribution of an anti-L1CAM antibody administered to cynomolgus monkey indicates favorable safety profile of L1CAM-targeting therapies
Presenter: Jacques Gaudreault
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
2905 - Pharmacokinetic drug-drug interaction between mitotane and etoposide in the treatment of adrenocortical carcinoma
Presenter: Anne Jouinot
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
2597 - Real-world dosing of regorafenib (REG) in metastatic colorectal cancer (mCRC): final results from the prospective, observational CORRELATE study
Presenter: Juan Manuel O'Connor
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
2663 - Safety and efficacy of trifluridine/tipiracil (FTD/TPI) in metastatic colorectal cancer (mCRC) patients according to previous treatment with regorafenib in the international phase 3b PRECONNECT study
Presenter: Julien Taieb
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1670 - Treatment pattern and outcomes of trifluridine/tipiracil therapy for metastatic colorectal cancer in the real-world data from the JFMC50 study
Presenter: Takeshi Kawakami
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1088 - Phase II trial to evaluate efficacy and tolerance of regorafenib monotherapy in patients (pts) over 70 with previously treated metastatic colorectal adenocarcinoma (mCRC) FFCD 1404 - REGOLD
Presenter: thomas Aparicio
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
2548 - Prospective Evaluation of Regorafenib Dose Escalation Strategy with Low Starting Dose in Patients with Colorectal Cancer
Presenter: Toshiki Masuishi
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
3244 - Regorafenib for metastatic colorectal carcinoma: a registry-based analysis
Presenter: Katerina Kopeckova
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract