- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Evaluating age as a factor for survival and quality of life in patients with BRAF V600E-mutant metastatic colorectal cancer treated with encorafenib + cetuximab ± binimetinib: subanalysis of BEACON CRC (Auditorium A; Level 0) - May 12, 2022 - Abstract #ESMOGI2022ESMO_GI_524;
Methods BEACON CRC was a randomized, open-label, phase 3 study comparing enco+cetux±bini and investigator's choice of irinotecan+cetux or FOLFIRI+cetux (control) in patients with previously treated BRAF V600E-mutant mCRC...This subanalysis is limited by the low number of patients. Further analyses are warranted to compare these age groups when treated with targeted therapies for mCRC.
- |||||||||| Avastin (bevacizumab) / Roche, Erbitux (cetuximab) / Eli Lilly, EMD Serono, Vectibix (panitumumab) / Amgen, Takeda
Anti-EGFR antibodies may get benefit as first-line treatment in metastatic right-sided colon cancer () - May 12, 2022 - Abstract #ESMOGI2022ESMO_GI_349;
Conclusions Right sided mCRC with combined RAS/RAF wild &Her2+ve &VEGF -ve expression did not benefitted from chemotherapy plus anti-VEGF as first-line setting so, we suggest that this group of patients may benefit from chemotherapy plus anti EGFR antibodies ± Her2 target therapy in first-line setting and this could be proven in future works that could help in risk adapted therapy. The primary tumor sidedness may not the only surrogate marker for selecting first-line targeted therapy in mCRC.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Association of MSS/MSI-RNF43 molecular subtypes and clinical outcome of metastatic BRAF-V600E colorectal cancer patients treated with anti-BRAF/EGFR ± combinatorial therapies (Auditorium A; Level 0) - May 12, 2022 - Abstract #ESMOGI2022ESMO_GI_172;
P3
To further demonstrate the biological impact of the identified RNF43 missense mutations, we performed luciferase reporter assays with ectopic expression of the RNF43 mutants and immunohistochemical analysis. Conclusions In summary, this study shows that the MSI/MSS-RNF43 molecular subtypes emerge as a potential stratification biomarker for CRCBRAF-V600E patients treated with anti-BRAF/EGFR ± combinatorial therapies and uncovers the crosstalk between the MAPK and WNT/β-catenin pathways as a new therapeutic avenue to be exploited in this setting.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Evidence of therapeutic effectiveness of III line cetuximab rechallenge in appropriately selected patients: finding from long-term follow-up of CRICKET and CAVE trials (Auditorium A; Level 0) - May 12, 2022 - Abstract #ESMOGI2022ESMO_GI_171;
In fact, after an anti-EGFR free window, that reduces the number of resistant cancer cell clones, re-treatment with the anti-EGFR monoclonal antibodies cetuximab or panitumumab may have antitumor activity...From the initial population of 77 and 28, respectively, 33 patients with RAS WT liquid biopsy at baseline from CAVE and 13 with the same characteristics from CRICKET, that received a third-line cetuximab rechallenge therapy (combined with irinotecan in CRICKET and with avelumab in CAVE), were analyzed...In particular combination with avelumab is associated with 2-year OS survival rate of 1 out of 5 patients. Randomized trials on larger number of patients are currently ongoing.
- |||||||||| Vectibix (panitumumab) / Amgen, Takeda
Modified FOLFOXIRI plus panitumumab (mFOLFOXIRI/PAN) versus mFOLFOX6/PAN as initial treatment of unresectable RAS/BRAF wild-type metastatic colorectal cancer (mCRC) patients: results of the phase III randomized TRIPLETE study by GONO (Auditorium A; Level 0) - May 12, 2022 - Abstract #ESMOGI2022ESMO_GI_170;
P3
Background The association of a chemotherapy doublet (FOLFOX/FOLFIRI) with an anti-EGFR monoclonal antibody (cetuximab or panitumumab) is an upfront option for the treatment of RAS and BRAF wt mCRC patients...Methods TRIPLETE is a prospective, open label, phase III trial in which previously untreated patients with unresectable RAS and BRAF wt mCRC were randomized to receive mFOLFOX6/pan (arm A) or mFOLFOXIRI (irinotecan 150 mg/sqm, oxaliplatin 85 mg/sqm, L-leucovorin 200 mg/sqm, 5-fluoruracil 2400 mg/sqm 48 h infusion)/pan (arm B) up to 12 cycles, followed by 5FU/LV/pan until disease progression...Clinical trial info: NCT03231722. Conclusions The intensification of the upfront chemotherapy backbone in combination with panitumumab in molecularly selected and mostly (88%) left-sided mCRC patients does not provide any benefit in terms of treatment activity at the price of a non-negligible increase in gastrointestinal toxicity.
- |||||||||| Avastin (bevacizumab) / Roche, Erbitux (cetuximab) / Eli Lilly, EMD Serono
Discussant: SO-16, SO-17 (Auditorium B; Level 0) - May 12, 2022 - Abstract #ESMOGI2022ESMO_GI_114;
Conclusions The intensification of the upfront chemotherapy backbone in combination with panitumumab in molecularly selected and mostly (88%) left-sided mCRC patients does not provide any benefit in terms of treatment activity at the price of a non-negligible increase in gastrointestinal toxicity. Learning Objectives: SO-16: FIRE-4 (AIO-KRK-0114): Randomized study for a switch maintenance concept with 5-FU plus bevacizumab after induction treatment with FOLFIRI plus cetuximab versus continued treatment with FOLFIRI plus cetuximab-secondary endpoint - Volker Heinemann, et al SO-17: A randomized, open-label, multicenter, phase 3 study of high-dose vitamin C plus FOLFOX +/- bevacizumab versus FOLFOX +/- bevacizumab as first-line treatment in patients with unresectable metastatic colorectal cancer - Feng Wang, et al
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Herceptin (trastuzumab) / Roche
Journal: Efficient spontaneous site-selective cysteine-mediated toxin attachment within a structural loop of antibodies. (Pubmed Central) - May 10, 2022
Our unique approach allows the generation of therapeutic ADCs with controlled chemical composition, which facilitates the optimization of their pharmacological activity. This strategy for directional coupling could in the future simplify the construction of ADCs with double payloads ("dual warheads") introduced with orthogonal techniques.
- |||||||||| Avastin (bevacizumab) / Roche, Erbitux (cetuximab) / Eli Lilly, EMD Serono, Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer
Journal, IO biomarker: The Evolving Treatment Landscape in BRAF-V600E-Mutated Metastatic Colorectal Cancer. (Pubmed Central) - May 10, 2022
The phase III BEACON clinical trial confirmed the BRAF/EGFR inhibitor combination of encorafenib/cetuximab as the new standard of care for BRAF-V600E mCRC after at least one previous line of systemic therapy. Novel approaches for managing BRAF-V600E mCRC include, among others, triple combinations of BRAF inhibitors and anti-EGFR antibodies combined with immune checkpoint inhibitors in the microsatellite instability population and evaluation of the encorafenib/cetuximab treatment in combination with standard chemotherapy with bevacizumab in the first-line setting.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Herceptin (trastuzumab) / Roche, Perjeta (pertuzumab) / Roche
Enrollment closed, Enrollment change, Surgery, Metastases: SWOG S1613: S1613, Trastuzumab and Pertuzumab or Cetuximab and Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic HER2/Neu Amplified Colorectal Cancer That Cannot Be Removed by Surgery (clinicaltrials.gov) - May 10, 2022
P2, N=240, Active, not recruiting,
N=40 --> 24 | Trial primary completion date: Jan 2022 --> Aug 2021 Recruiting --> Active, not recruiting | N=130 --> 240
- |||||||||| Avastin (bevacizumab) / Roche, Erbitux (cetuximab) / Eli Lilly, EMD Serono
Preclinical, Journal, Monotherapy: Effectiveness of Hyperthermia as Monotherapy and Adjuvant Therapy Approaches Against an In Vitro Model of Colorectal Carcinoma. (Pubmed Central) - May 7, 2022
Trial completion date: Dec 2022 --> Apr 2023 | Trial primary completion date: Dec 2022 --> Apr 2023 We have developed an optimized experimental hyperthermic protocol, as a promising monotherapy and/or adjuvant therapy approach, with the capacity to potentiate chemotherapeutic as well as targeted drug-induced cytotoxicity against a model of colorectal carcinoma, to a variable degree.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Herceptin (trastuzumab) / Roche
Journal: Triple targeting of HER receptors overcomes heregulin-mediated resistance to EGFR blockade in colorectal cancer. (Pubmed Central) - May 6, 2022
Current treatment options for patients with advanced colorectal cancers include anti-EGFR/HER1 therapy with the blocking antibody cetuximab...Here, we provide evidence that triple-HER receptor blockade based on a newly developed bispecific EGFR×HER3-targeting antibody (scDb-Fc) together with the HER2-blocking antibody trastuzumab effectively inhibited HRG-induced HER receptor phosphorylation, downstream signaling, proliferation, and stem cell expansion of DiFi and LIM1215 colorectal cancer cells...Importantly, growth suppression by triple HER targeting was recapitulated in primary KRAS wild-type patient-derived organoid (PDO) cultures exposed to HRG. Collectively, our results provide strong support for a pan-HER receptor blocking approach to combat anti-EGFR therapy resistance of KRAS wild-type CRC tumors mediated by the upregulation of HRG and/or HER2/HER3 signaling.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Journal: Reactivity of NK Cells Against Ovarian Cancer Cells Is Maintained in the Presence of Calcium Phosphate Nanoparticles. (Pubmed Central) - May 6, 2022
We explored these interactions in coculture systems consisting of NK cells, OC cells, CaP-NPs, and therapeutic Cetuximab antibodies (anti-EGFR, ADCC-inducing antibody)...Therapeutic antibody coupled to functionalized CaP-NPs maintained substantial levels of antibody-dependent cellular cytotoxic activity. Our study provides a cell biological basis for the application of functionalized CaP-NPs in immunologic anti-cancer therapies.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Herceptin (trastuzumab) / Roche
Journal: Palladium-Mediated Incorporation of Carboranes into Small Molecules, Peptides, and Proteins. (Pubmed Central) - May 6, 2022
Conjugated proteins maintain their activity in cell-based functional assays in HER2-positive BT-474 cell lines. This approach enables the rapid incorporation of carborane moieties into small molecules, peptides, and proteins for further exploration in boron neutron capture therapy, which requires the targeted delivery of boron-dense groups.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Trial completion date, Trial initiation date, Trial primary completion date, Metastases: Cetuximab for the Treatment of Advanced Unresectable or Metastatic Chordoma (clinicaltrials.gov) - May 5, 2022
P2, N=29, Not yet recruiting,
Active, not recruiting --> Completed Trial completion date: Sep 2022 --> Sep 2024 | Initiation date: Sep 2021 --> Sep 2022 | Trial primary completion date: Sep 2022 --> Sep 2024
- |||||||||| Bavencio (avelumab) / EMD Serono, Erbitux (cetuximab) / Eli Lilly, EMD Serono
Trial completion date, Trial initiation date, Trial primary completion date, Metastases: CAVE 2: CAVE-2 GOIM Study: a Clinical Study of the Combination of Avelumab Plus Cetuximab as Rechallenge Strategy (clinicaltrials.gov) - May 5, 2022
P2, N=173, Not yet recruiting,
Trial completion date: Sep 2022 --> Sep 2024 | Initiation date: Sep 2021 --> Sep 2022 | Trial primary completion date: Sep 2022 --> Sep 2024 Trial completion date: Apr 2025 --> Jul 2025 | Initiation date: Apr 2022 --> Jul 2022 | Trial primary completion date: Apr 2025 --> Jul 2025
- |||||||||| Review, Journal, PD(L)-1 Biomarker, IO biomarker: Targeted Therapy for Colorectal Cancer. (Pubmed Central) - May 4, 2022
Patients with mCRC with KRAS/NRAS/BRAF wild-type left-sided tumors may benefit from epidermal growth factor receptor (EGFR) inhibition with either cetuximab or panitumumab, in conjunction with chemotherapy...The vascular endothelial growth factor (VEGF) inhibitor bevacizumab can serve as an alternative to EGFR inhibitors in right-sided tumors or second-line therapy...Triple combination therapy with cetuximab, the BRAF inhibitor encorafenib, and the MEK kinase inhibitor binimetinib has extended overall survival by about 3 months compared with chemotherapy alone...The KEYNOTE-177 trial demonstrated that therapy with single-agent pembrolizumab improved progression-free survival by 8 months compared with FOLFOX or FOLFIRI and with or without EGFR inhibition. At this time, targeted therapy should only be used in patients with unresectable metastatic disease.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Trial completion date, Trial primary completion date, Surgery, Metastases: Cetuximab Before Surgery in Treating Patients With Aggressive Locally Advanced Skin Cancer (clinicaltrials.gov) - May 4, 2022
P=N/A, N=15, Active, not recruiting,
These findings support pembrolizumab as an efficacious first-line therapy in patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer. Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Dec 2021 --> Dec 2022
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Observational data, Review, Journal: Systematic review of randomised clinical trials and observational studies for patients with RAS wild-type or BRAF-mutant metastatic and/or unresectable colorectal cancer. (Pubmed Central) - May 3, 2022
In BEACON CRC, overall survival (OS) was significantly longer for patients receiving encorafenib plus cetuximab ± binimetinib when compared with irinotecan/FOLFIRI plus cetuximab as second- and third-line therapy...Patients with BRAF-mutant mCRC have worse outcomes with conventional therapy vs patients with BRAF wild-type tumours. BRAF inhibitors in conjunction with anti-EGFR therapy improves outcomes for patients with BRAF-mutant mCRC vs conventional therapy or a BRAF inhibitor alone.
- |||||||||| Avastin (bevacizumab) / Roche, Erbitux (cetuximab) / Eli Lilly, EMD Serono, Vectibix (panitumumab) / Amgen, Takeda
Review, Journal: Treatment sequencing of metastatic colorectal cancer based on primary tumor location. (Pubmed Central) - Apr 30, 2022
Patients whose primary tumor originates from the left side of the colon and whose tumor's genome encodes wild-type RAS and BRAF should be offered cetuximab or panitumumab in the first-line treatment of metastatic disease or in subsequent lines...Specifically, an aggressive initial approach with FOLFOXIRI plus bevacizumab is a treatment option in right-sided tumors under investigation. This report reviews the available data for the treatment of metastatic colorectal cancer according to the location of the primary tumor and proposes the optimal treatment sequencing strategy incorporating the site of origin of the tumor and molecular information into the decision-making process.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Clinical, Journal: Nephrotic syndrome induced by cetuximab in a patient with metastatic colorectal cancer. (Pubmed Central) - Apr 30, 2022
Therefore, drugs targeting epidermal growth factor receptor (EGFR) monoclonal antibody were thought to trigger nephrotic syndrome by causing glomerular damage. As a result, physicians using EGFR monoclonal inhibitors should be very careful about renal functions and proteinuria in patients.
- |||||||||| cisplatin / Generic mfg.
Review, Journal, Combination therapy, PD(L)-1 Biomarker, IO biomarker: Application of Approved Cisplatin Derivatives in Combination Therapy against Different Cancer Diseases. (Pubmed Central) - Apr 30, 2022
An important approach for overcoming the drug resistance and reduction of toxicity of Cisplatin derivatives is the application of nanocarriers (polymers and liposomes), which provide improved targeted delivery, increased intracellular penetration, selective accumulation in tumor tissue, and enhanced therapeutic efficacy. The advantages of combination therapy are maximum removal of tumor cells in different phases; prevention of resistance; inhibition of the adaptation of tumor cells and their mutations; and reduction of toxicity.
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