Abstract 3808
Background
Immune-checkpoint blockade has shown anti-tumor activity in MSI mCRC patients only, thus, the research of more efficacious immunological strategies for colon cancer treatment is still open. GOLFIG, is a safe and active chemo-immunotherapy regimen designed on the basis of preclinical immune-oncological findings and evaluated in two subsequent Phase II and III trials in mCRC patients (J Clin Oncol, 2005,23:8950; J Immunother, 2014;37:26). This regimen combines gemcitabine + FOLFOX poly-chemotherapy with salgramostim (GM-CSF) and low dose sc. aldesleukin, to improve both cross-priming and T-cell effector anti-tumor response. Here we report a fifteen-year retrospective analysis of all patients undergone this therapeutic approach.
Methods
This is a multi-institutional real-life study including one hundred-seventy-nine mCRC patients receiving GOLFIG regimen between October 2001 and November 2018 with a median follow up of 120 months. The treatment was administered to 62 patients (GOLFIG-2 trial, EUDRACT: 2005-003458-81) as a first-line and to 117 patients as second/third-line (49 enrolled in the GOLFIG-1 phase II trial and 68 as real life). Kaplan-Meier and Cox-regression were carried-out to relate their PFS and OS with sex, age, sidedness, RAS mutational status, previous treatment lines, baseline clinical parameters and treatment-related irAEs.
Results
We recorded a PFS and OS of 15.3 (95%CI:10.4-20.2) and 24.6 (95%CI:19.07-30.14) months, respectively, with 10% of the patients surviving more than ten years. Patients’ outcome did not correlate with sex, sidedness and RAS. First line GOLFIG confirmed superiority over FOLFOX in term of PFS (HR = 0.58 p = 0.006) and OS (HR = 0.69, P = 0.06) (updated from GOLFIG-2 trial). Patients in first-line showed a longer PFS (HR = 0.69; p = 0.041) compared with the others, with no difference in OS. On the overall, a longer PFS and OS correlated with baseline neutrophil counts ≤ 4,500 cells/µl (HR:0.32; P = 0.003) and occurrence of irAEs (HR = 0.36; P = 0.0001) recorded in 24% of the cases.
Conclusions
These results confirm that the GOLFIG regimen is a reliable therapy for pretreated mCRC patients and offer the rationale to design combination trials with immune-checkpoint blockade.
Clinical trial identification
1) GOLFIG-2 phase III trial; EudraCT: 2005-003458-81 2) GOLFIG-1 phase II trial; EudraCT no available, start July 2001.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Italian Ministry of Education and Research (MIUR) (2009EHW394). Private grant from the “Associazione Culturale Federico II,” and from the “Associazione Riuniti Calabria Oncologia (ARCO)”.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2115 - Preclinical in vivo screening to predict responder patients depend on EGFR status
Presenter: Yejin Kim
Session: Poster Display session 3
Resources:
Abstract
3349 - Interplay between miR-17-5p and MALAT-1 Shapes The Cytokine Storm in Triple Negative Breast Cancer (TNBC) Tumor Microenvironment
Presenter: Raghda Soliman
Session: Poster Display session 3
Resources:
Abstract
4014 - Clinical verification on the relationship between lipid metabolism and the immune microenvironment of breast cancer
Presenter: Wataru Goto
Session: Poster Display session 3
Resources:
Abstract
4158 - The clinical and transcriptional signatures of human CD204 reveal an applicable marker for tumor associated macrophage in breast cancer
Presenter: Yunjie He
Session: Poster Display session 3
Resources:
Abstract
5392 - Activated effector T cells co-expressing multiple inhibitory receptors (IRs) are enriched in the tumor immune microenvironment in high grade serous ovarian cancer (HGSOC)
Presenter: Alice Bergamini
Session: Poster Display session 3
Resources:
Abstract
2617 - Oncolytic reovirus as a new anti-tumor strategy in castration resistant prostate cancer
Presenter: Yunlim Kim
Session: Poster Display session 3
Resources:
Abstract
2995 - Dysregulation of helper T lymphocytes in esophageal squamous cell carcinoma (ESCC) patients is highly associated with aberrant production of miR-21
Presenter: Ali Memarian
Session: Poster Display session 3
Resources:
Abstract
3597 - Myeloid derived suppressor cells but not regulatory T cells are associated with adaptive immunity and clinical outcomes in anal squamous cell carcinoma
Presenter: Christophe Borg
Session: Poster Display session 3
Resources:
Abstract
3430 - Evaluation of immune responses among responders (R) and non-responders (non-R) in a humanized mouse model with colorectal cancer (CRC) xenografts treated with combination immunotherapy
Presenter: Juan Marín Jiménez
Session: Poster Display session 3
Resources:
Abstract
1995 - ¬¬Advanced melanoma patients with high CD16+ macrophages have better response and survival to anti-PD-1 based immunotherapy
Presenter: Hansol Lee
Session: Poster Display session 3
Resources:
Abstract