^
Association details:
| Biomarker: | RAS wild-type |
|---|---|
| Cancer: | Colorectal Cancer |
| Drug: | Erbitux (cetuximab) (EGFR inhibitor) + Bavencio (avelumab) (PD-L1 inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
FOLFIRI + Cetuximab + Avelumab RAS Wild-type CRC
Excerpt:
...- RAS wild-type tumour status (KRAS and NRAS exon 2, 3, 4) (proven in the primary tumour or metastasis)...
Trial ID:
Source:
Title:
Avelumab added to FOLFIRI plus Cetuximab followed by Avelumab maintenance in patients with previously untreated RAS wild-type colorectal cancer - The phase II FIRE-6-Avelumab study
Excerpt:
...RAS wild-type tumour status (KRAS and NRAS, exon 2, 3, 4) and BRAF wild-type tumour status (V600, exon 15) (proven in the primarytumour or metastasis)3. ...
Trial ID:
More C2 evidence
Source:
Title:
Avelumab and Cetuximab and FOLFOXIRI in metastatic colorectal cancer Avelumab più Cetuximab più FOLFOXIRI nel carcinoma del colonretto metastatico
Excerpt:
......
Trial ID:
Source:
Title:
Avelumab Combined With Cetuximab and Irinotecan for Treatment Refractory Metastatic Colorectal Microsatellite Stable Cancer
Excerpt:
...- Histologically proven metastatic colorectal adenocarcinoma, refractory to standard chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan) and anti-EGFR treatment (only for RAS WT tumor)...
Trial ID:
Less C2 evidence
Source:
Title:
2237P - Avelumab (AVE), cetuximab (CET) and irinotecan (IRI) for treatment refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC): Translational analyses of the AVETUXIRI phase II trial
Published date:
10/16/2023
Excerpt:
MSS, chemorefractory (anti-EGFR refractory if RAS wt) mCRC patients (pts) were enrolled (RAS wt: 28 pts, RAS mut: 27 pts) and treated with CET and IRI from week 1(W1) and AVE from W3...Among 55 treated pts, 95 biopsies (W0: 39, W3: 29, W11: 27) were available for MIF (table: W0 results). On 23 pts (1st stage), upregulation of adaptive immune response signature was associated with tumor shrinkage, PFS>6 and OS>12 months (p. adj= 0.00)...Independently of RAS mutation, existing adaptive immune response within metastases is associated with treatment benefit.
Secondary therapy:
irinotecan
Trial ID:
Source:
Title:
Cetuximab as third-line rechallenge plus either irinotecan or avelumab is an effective treatment in metastatic colorectal cancer patients with baseline plasma RAS/BRAF wild-type circulating tumor DNA: Individual patient data pooled analysis of CRICKET and CAVE trials
Published date:
03/07/2023
Excerpt:
For the whole 46 patient population, median PFS (mPFS) was 3.9 months (95% Confidence Interval, CI 3.0–4.9) with median OS (mOS) of 16.9 months (95% CI 11.7–22.1). For CRICKET patients, mPFS was 3.9 months (95% CI 1.7–6.2); mOS was 13.1 months (95% CI 7.3–18.9) with OS rates at 12, 18, and 24 months of 62%, 23%, and 0%, respectively. For CAVE patients, mPFS was 4.1 months (95% CI 3.0–5.2); mOS was 18.6 months (95% CI 11.7–25.4) with OS rates at 12, 18, 24 months of 61%, 52%, 21%, respectively....Third-line cetuximab rechallenge in combination with either irinotecan or avelumab in RAS/BRAF WT ctDNA mCRC patients represents a promising therapy.
DOI:
https://doi.org/10.1002/cam4.5699
Source:
Title:
Translational analysis and final efficacy of the AVETUX trial - Avelumab, cetuximab and FOLFOX in metastatic colorectal cancer
Published date:
12/20/2022
Excerpt:
The AVETUX trial aimed to combine the PD-L1 antibody avelumab with the standard of care chemotherapy combination FOLFOX and the anti-EGFR antibody cetuximab….In total, 43 patients were treated of which 39 patients were confirmed as RAS/BRAF wildtype in central tissue review and finally response evaluated....In summary, we report the final overall survival of the AVETUX trial and propose T cell clonality and diversity as a potential marker to predict response to chemo-immunotherapy combinations in MSS mCRC...
DOI:
10.3389/fonc.2022.993611
Trial ID:
Source:
Title:
424P - Avelumab added to FOLFIRI plus cetuximab followed by avelumab maintenance in patients with previously untreated RAS wild-type colorectal cancer: The phase-II FIRE-6 (AIO KRK-0118)
Published date:
09/05/2022
Excerpt:
Median PFS was 7.0 months in 47 evaluable patients. Overall response rate was 73.2% with a disease control rate of 87.5%....FIRE-6 avelumab confirms the efficacy with respect to tumor response and disease control of FOLFIRI plus cetuximab as first-line treatment of patients with RAS wild-type mCRC.
Secondary therapy:
FOLFIRI
Trial ID:
Source:
Title:
Interim analysis of the phase II AVETUXIRI trial: Avelumab combined with cetuximab and irinotecan for treatment of refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC).
Published date:
05/26/2022
Excerpt:
No unexpected safety signals were observed. 3/10 tumor responses were observed in cohort A, 0/13 in cohort B. DCR was 60.0% and 61.5% in cohort A and B, respectively. 6-months PFS and 12-months OS rates were respectively 40.0% and 50.0% (cohort A) and 38.5% and 46.2% (cohort B). Independently of RAS mutation, patients with a high IS (metastasis biopsy, baseline) had significantly higher tumor shrinkage (OR = 18.67 p = 0.019), median PFS (6.9 vs 3.4 months; HR = 0.16, p = 0.002) and median OS (13.7 vs 7.9 months, HR = 0.26, p = 0.009). Similarly, tumor shrinkage and survival outcome (PFS > 6 months, OS > 12 months) were associated with upregulation of an adaptive immune response signature (including Th1, chemokine, adhesion molecules, immune checkpoints and T-cell activation genes, p. adj = 0.009) and the GSEA hallmark of epithelial to mesenchymal transition (p. adj = 0.045). AVETUXIRI met its preliminary primary efficacy endpoint for RAS-wt mCRC pts, justifying its current continuation. Encouraging survival data observed in RAS-mut cohort allow the opening of a new cohort (PFS as primary endpoint). IS and adaptive immune response signature evaluated on metastases biopsies were associated with treatment efficacy and survival.
Trial ID:
