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  • American Society of Clinical Oncology (ASCO)  (3)
  • Comas, Raquel  (3)
  • 1
    Online Resource
    Online Resource
    Impact of WNT/B-catenin alterations and metastasis location among patients with metastatic colorectal cancer (mCRC) treated with immune checkpoint inhibitors (ICI) combinations.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 3573-3573
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 3573-3573
    Abstract: 3573 Background: Emerging evidence suggests that WNT mutations and liver/peritoneal metastases in mCRC may have an immunosuppressive role that could affect ICI activity. Aim: To evaluate the impact of WNT alterations and liver/peritoneal metastasis among patients with mCRC treated with ICi. Methods: Patients from Vall d’Hebron Hospital, with mCRC treated with ICI from 2017-2022 were included. WNT alterations (APC, AXIN1/2, CTNNB1, FBXW7, EPHB2, RNF43 and SOX9) were evaluated using NGS (tissue). Clinical outcomes were calculated using survival Kaplan-Meier curves. Patients' characteristics were collected retrospectively. Results: Overall, 104 patients were included (66 MSI patients and 38 MSS patients). Among MSI patients, median age was 63 years (22-95), with 53% female, and 64% of patients received immunotherapy in 1st or 2nd line. Regarding tumor characteristics, 72% were right-sided and 82% harbored WNT alterations. 75% of patients presented with liver/peritoneal metastases. Patients with WNT mutations and peritoneal/liver metastases exhibit lower ORR (46% vs 57% p 0.5 and 45% vs 75%, p 0.03 respectively). Peritoneal/liver metastases were associated with lower PFS (HR 3.6 CI95% 1.27-10.24 p 0.02 respectively). Overall, tumors with WNT pathway alterations tend to have shorter PFS and OS. Liver metastases were associated with lower OS (NR vs 34 months HR 2.49 CI95% 1.01-6.17 p 0.05). Table summarizes outcomes. Among MSS patients, median age was 57 years (41-75), with 25% female and 92% of patients receiving immunotherapy 〉 = 3rd line. Regarding tumor characteristics, 78% were left-sided and 90% harboured WNT alterations. 79%, of patients presented with liver or peritoneal metastases. WNT mutations were not associated with ORR, patients without liver/peritoneal metastases tend to have higher ORR (12.5% vs 3.3% p 0.335). Patients with WNT alterations had worse PFS (9.23 vs 1.87 months, p 0.12), and liver metastases were associated with lower PFS (6.98 vs 1.79 months HR 2.87 CI95% 1.17-7.09 p:0.02). Regarding OS, tumors harboring WNT alterations have shorter OS (8.4 vs 12 months p 0.63). The presence of liver or peritoneal metastases was associated with lower OS (NR vs 7.85 months HR 3.69 CI95% 1.09-12.55 p: 0.04). Conclusions: In our cohort, WNT pathway mutations, and liver metastases were associated with worse ORR, PFS, and OS regardless of MSI status. These findings need further validation in a prospective cohort. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.3573
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 2
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    Molecular characterization and subsequent treatments after encorafenib-cetuximab +/- binimetinib in BRAF V600E-mutated colorectal cancer.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 3562-3562
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 3562-3562
    Abstract: 3562 Background: The BRAF-V600E mutation confers poor prognosis in patients with mCRC. E-C+/-B improve clinical outcomes compared with standard of care. Data about subsequent treatment lines and the impact of NGS in the treatment choice after the BRAF targeted treatment are still limited. We have analyzed the global overall survival (OS) and the impact of NGS to guide subsequent treatments (approved targeted therapies (TT) or clinical trials (CT)) after E-C+/-B. Methods: Patients who had received E-C+/-B were included. Clinical data was collected prospectively. Tissue NGS was performed prospectively and retrospectively using an in-house NGS panel (VHIO-300). Subsequent treatments’ clinical outcomes were described. Percentage of patients who received TT or CT based on NGS results is reported. Clinical outcomes were calculated using survival Kaplan-Meier curves. Results: From 2017 to 2021, 59 patients with refractory mCRC received E-C+/-B at our institution. 50 patients have already progressed to the BRAF inhibitor combination and 9 patients remain on BRAF inhibitor treatment. Tumor tissue for NGS testing before BRAF inhibitor treatment was available in 70% of patients (41/59). BRAF-V600E mutation was confirmed in tissue using ddPCR in all patients. The most frequent alterations were: BRAF-V600E 93%, TP53 64%, RNF43 30%, APC 20%, PIK3CA 14%, NOTCH1/2 9%, RANBP2 8%, PTEN 8%, MET amplification 5%. MSI incidence was 10%, 2 out of 6 (33%) received subsequent immunotherapy. After the BRAF inhibitor combination, 23 patients (38%) did not receive subsequent treatment (clinical deterioration or death). The 27 remaining patients (62%) received 41 subsequent treatments (37% of them were TT or CT). Median subsequent lines after the BRAF inhibitor combination were 1 (0-3). NGS led to targeted therapy in 20% of the patients: BRAF inhibitors combos (20%), microtubule inhibitors (13%), antiPD1 (13%), NOTCH inhibitors (6%), and MET inhibitor (6%). ORR among patients who received matched TT or CT was 6% and DCR (CR+PR+SD) was 47%. The median OS after the BRAF inhibitor was 3.8 months; 10.1 months vs 3.0 months (HR 0.43 (95%CI 0.2-0.95), p = 0.04) for those patients who received TT or CT vs patients who did not receive TT or CT. When MSI patients were excluded mOS was 5.2 vs 3.0 months (HR 0.61 (95%CI 0.27-1.37), p = 0.23) respectively. There were no differences in terms of OS regarding the number of previous lines (0-1 vs 2-3, HR 0.75 (95%CI 0.4-1.42), p = 0.37) or with the BRAF inhibitor regimen used (E-C vs E-C-B) (HR 0.84, (95%CI 0.44-1.6), p = 0.61) Conclusions: This study suggests that patients with BRAF-V600E mutant mCRC could have benefit when treated with TT and/or in CT after a BRAF inhibitor-based therapy, including immunotherapy. Genomic analysis might help to guide subsequent treatments. Because of molecular heterogeneity, these patients should be discussed in Molecular Tumor Boards.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.3562
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 3
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    Online Resource
    Impact of circulating tumor DNA (ctDNA) mutant allele fraction in response to anti-angiogenic therapy in RAS -mutant metastatic colorectal cancer (mCRC): Clinical data in the first-line setting and correlation in patient-derived xenograft (PDX) models.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 3560-3560
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 3560-3560
    Abstract: 3560 Background: Currently, there are no well-established biomarkers available to select mCRC patients (pts) who will benefit most from antiangiogenic therapy. RAS mutant (mt) allele fraction in plasma (plMAF) is an independent prognostic factor in mCRC. Preliminary data from our group suggests the possible predictive role of plMAF in RAS mt pts treated with 1st line chemotherapy (ct) +/- bevacizumab (bev). Methods: Data prospectively/retrospectively collected from RASmt mCRC pts who received 1 st line ct+/-bev treatment in our center, selecting the subset of pts with plMAF sample evaluable with digital PCR (BEAMing) at baseline. Pts were stratified as high (≥ 5.8%) or low ( 〈 5.8%) plMAF, based on a previously established prognostic cutoff (Elez et al, Mol Onc 2019). We investigated the associations between clinic-pathological variables, overall survival (OS), and progression-free survival (PFS) stratified by plMAF RAS levels using Cox regression models. OS and PFS were calculated by Kaplan-Meier method. Murine PDX were developed from mCRC pts including models from patients with KRASG12/G13 mutations to explore recapitulation of the clinical findings. Results: From October ‘17 to December ‘21, 102 basal plasma samples were analyzed by BEAMing. 47 pts (46%) were classified as high, 39 pts (38%) as low, and 16 (16%) as no-mt detected by BEAMing (non-shedding). OS was significant longer in low plMAF pts than in high plMAF pts (median OS 15.9 vs 37.1 months (mo); HR 0.43; p = 0.001). In high plMAF pts, a trend towards a better PFS was observed in those pts treated with ct+bev compared to ct alone (median 9.4 vs 6.1 mo; HR 0.6; p = 0.18). No differences were observed in low plMAF pts treated with ct +/- bev (median 14.5 vs 14.9 mo; HR 1.2; p = 0.58). Results were not modified when adjusted by the presence of liver metastases. The multivariate PFS model showed no association between RAS plMAF and clinicopathological variables, except for treatment benefit with ct+bev and better outcomes in pts with resectable liver metastases. Interestingly, human ctDNA in one murine PDX model from non-shedding pt was not detectable, whereas human ctDNA was present in another PDX model with a plMAF of 36.2%. Conclusions: This study suggests that plMAF could be a promising predictive biomarker of response to bev in 1 st line RASmt mCRC, but more pts need to be analyzed to confirm this effect. Our results confirm the prognostic role of RASmt plMAF in mCRC. plMAF could partially depend on tumor cell shedding degree and characteristics on the tumor vasculature architecture, this is being investigated in ongoing imaging studies and PDX models. These models will also help to understand the biology behind tumor response to bev and its connection with ctDNA shedding.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.3560
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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    Online Resource
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