444TiP Trial in progress: A phase Ib study of sotorasib, a selective KRAS G12C inhibitor, in combination with panitumumab and FOLFIRI in treatment naïve and previously treated metastatic colorectal cancer (CodeBreaK 101)

Masuishi, T.; Kuboki, Yasutoshi; Fakih, Marwan; Strickler, John H.; Furqan, Muhammad; Kim, E.J.; Cardona, Panli; Tran, Qui; Chan, Emily; Hong, D.S.

doi:10.1016/j.annonc.2022.07.1865

Cited by 3 publications

(3 citation statements)

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“…In conclusion, our data suggest that, currently, in the absence of approved targeted agents in the first-line setting, when a doublet chemotherapy is chosen, irinotecan-based regimens should be preferred, especially in patients without lung metastases. Moreover, possible synergic effects should be taken into consideration if combinations of 'chemotargeted' therapies with novel KRAS G12C -inhibitors are tested in clinical trials, since these new drugs might either potentiate the effect of less efficacious regimens, such as oxaliplatinbased doublets, or further enhance the beneficial effect of more efficacious regimens, such as those that are irinotecan-based [21].…”

Section: Discussionmentioning

confidence: 99%

Irinotecan- vs. Oxaliplatin-Based Doublets in KRASG12C-Mutated Metastatic Colorectal Cancer—A Multicentre Propensity-Score-Matched Retrospective Analysis

Formica

Morelli

Conca

et al. 2023

Cancers

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Background: KRASG12C-mutated metastatic colorectal cancer (mCRC) has recently been recognized as a distinct druggable molecular entity; however, there are limited data on its sensitivity to standard chemotherapy. In the near future, the combination of chemotherapy plus a KRASG12C-inhibitor might become the standard of care; however, the optimal chemotherapy backbone is unknown. Methods: A multicentre retrospective analysis was conducted including KRASG12C-mutated mCRC patients treated with first-line FOLFIRI or FOLFOX +/− bevacizumab. Both unmatched and propensity-score-matched analysis (PSMA) were conducted, with PSMA controlling for: previous adjuvant chemotherapy, ECOG PS, use of bevacizumab in first line, timing of metastasis appearance, time from diagnosis to first-line start, number of metastatic sites, presence of mucinous component, gender, and age. Subgroup analyses were also performed to investigate subgroup treatment–effect interactions. KRASG12D-mutated patients were analysed as control. Results: One hundred and four patients treated with irinotecan-(N = 47) or oxaliplatin-based (N = 57) chemotherapy were included. In the unmatched population, objective response rate (ORR) and median (m) progression-free and overall survival (mPFS and mOS) were comparable between the treatment arms. However, a late (>12 months) PFS advantage was observed with irinotecan (HR 0.62, p = 0.02). In the PSMA-derived cohort, a significant improvement with irinotecan vs. oxaliplatin was observed for both PFS and OS: 12- and 24-month PFS rates of 55% vs. 31% and 40% vs. 0% (HR 0.40, p = 0.01) and mOS 37.9 vs. 21.7 months (HR 0.45, p = 0.045), respectively. According to the subgroup analysis, interaction effects between the presence of lung metastases and treatment groups were found in terms of PFS (p for interaction = 0.08) and OS (p for interaction = 0.03), with a higher benefit from irinotecan in patients without lung metastases. No difference between treatment groups was observed in the KRASG12D-mutated cohort (N = 153). Conclusions: First-line irinotecan-based regimens provided better survival results in KRASG12C-mutated mCRC patients and should be preferred over oxaliplatin. These findings should also be considered when investigating chemotherapy plus targeted agent combinations.

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Section: Discussionmentioning

confidence: 99%

Irinotecan- vs. Oxaliplatin-Based Doublets in KRASG12C-Mutated Metastatic Colorectal Cancer—A Multicentre Propensity-Score-Matched Retrospective Analysis

Formica

Morelli

Conca

et al. 2023

Cancers

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“…The fluorouracil ± bevacizumab protocol is the standard maintenance treatment regimen for mCRC [ 29 , 30 ]. However, for mCRC patients with wild‐type RAS/BRAF who have achieved disease control after first‐line induction therapy with FOLFIRI combined with anti‐EGFR antibodies, how to choose the best maintenance therapy is still inconclusive [ 31 ].…”

Section: Chemotherapy For Crcmentioning

confidence: 99%

“…Therefore, multitarget combination therapy would be a more effective strategy for patients with KRAS G12C‐mutant mCRC. Additionally, the CodeBreaK300 phase III study [ 38 ] comparing sotorasib combined with panitumumab versus chemotherapy and the CodeBreaK101 study [ 31 ] investigating the efficacy of sotorasib plus panitumumab and the FOLFIRI regimen for first‐line treatment is currently in progress and the results are eagerly awaited.…”

Section: Targeted Therapy For Crcmentioning

confidence: 99%

Advances and prospects of drug clinical research in colorectal cancer in 2022

Liu

Cui

et al. 2023

Cancer Innovation

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Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer death worldwide. Clinical research results have provided more treatment opportunities for CRC patients, showing that an optimal combination of existing drugs and new drugs is needed to mitigate the burden of this disease. In this review, we have summarized recent advances in drug clinical research for CRC in 2022, including chemotherapy, targeted therapy, and immunotherapy, to find opportunities for substantial improvements in drug discovery and clinical development methods.

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Circulating tumour DNA analysis and new uses of anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer

Ruban,

Bolotina,

Karagodina

et al. 2024

Medicinskij alfavit

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Currently, tumour tissue biopsy to determine RAS/BRAF gene alterations, assess microsatellite instability status, and determine HER‑2/neu gene amplification/hyperexpression is the gold standard of diagnosis and allows the selection of optimal molecularly targeted therapy when considering treatment strategies for patients with metastatic colorectal cancer. However, biopsy does not fully reflect the existing intratumoural heterogeneity and clonal evolution of tumour cells, which can often be the cause of therapeutic failures. In recent years, liquid biopsy has attracted increasing attention as an additional and potentially alternative non-invasive tool for molecular tumour profiling. Assessment of circulating tumour DNA allows changes in the genetic status of the tumour to be monitored and the «burden» of disease to be measured dynamically in real time. Advances in liquid biopsy technology have led to promising new strategies for the management of patients with metastatic colorectal cancer in late-line therapy. The standard drug arsenal in this group of patients is limited to either repeat administration of previously effective therapy or regorafenib and the combination of trifluridine/tipiracil with bevacizumab, which are characterized by limited clinical activity. However, thanks to the discovery of the NeoRAS wild-type phenomenon and the rechallenge strategy of anti-EGFR monoclonal antibodies based on the study of clonal selection and evolution of tumour cells, the administration of epidermal growth factor inhibitors in a molecularly selected by liquid biopsy population is accompanied by good tolerability and efficacy. Numerous clinical studies are ongoing to further understand the mechanisms of tumour resistance and to develop new evidence-based treatment approaches in order to realise the concept of personalised medicine.

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444TiP Trial in progress: A phase Ib study of sotorasib, a selective KRAS G12C inhibitor, in combination with panitumumab and FOLFIRI in treatment naïve and previously treated metastatic colorectal cancer (CodeBreaK 101)

Cited by 3 publications

References 0 publications

Irinotecan- vs. Oxaliplatin-Based Doublets in KRASG12C-Mutated Metastatic Colorectal Cancer—A Multicentre Propensity-Score-Matched Retrospective Analysis

Irinotecan- vs. Oxaliplatin-Based Doublets in KRASG12C-Mutated Metastatic Colorectal Cancer—A Multicentre Propensity-Score-Matched Retrospective Analysis

Advances and prospects of drug clinical research in colorectal cancer in 2022

Circulating tumour DNA analysis and new uses of anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer

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