Diagnosis and Treatment of Metastatic Colorectal Cancer

JAMA, Journal Year: 2021, Volume and Issue: 325(7), P. 669 - 669

Published: Feb. 16, 2021

Importance

Colorectal cancer (CRC) is the third most common cause of mortality worldwide with more than 1.85 million cases and 850 000 deaths annually. Of new colorectal diagnoses, 20% patients have metastatic disease at presentation another 25% who present localized will later develop metastases.

Observations

for men women in United States, 53 200 projected 2020. Among people diagnosed cancer, approximately 70% to 75% survive beyond 1 year, 30% 35% 3 years, fewer 5 years from diagnosis. The primary treatment unresectable CRC systemic therapy (cytotoxic chemotherapy, biologic such as antibodies cellular growth factors, immunotherapy, their combinations.) Clinical trials completed past demonstrated that tailoring molecular pathologic features tumor improves overall survival. Genomic profiling detect somatic variants important because it identifies treatments may be effective. For 50% withKRAS/NRAS/BRAFwild-type tumors, cetuximab panitumumab (monoclonal epithelial factor receptor [EGFR]), combination can extend median survival by 2 4 months compared chemotherapy alone. However, 40% withKRASorNRASsequence variations (formerly termedmutations), effective targeted therapies are not yet available. 5% 10% withBRAF V600Esequence variations, BRAF EGFR inhibitors extended 9.3 months, 5.9 those receiving standard chemotherapy. microsatellite instability (the presence numerous insertions or deletions repetitive DNA units) mismatch repair deficiency, immunotherapy used first subsequent line has improved outcomes a 31.4 previously treated patients.

Conclusions Relevance

Advances facilitate ability direct specific patient subsets. Although cures remain uncommon, anticipate allows selection so derive benefit exposed toxicity ineffective therapies.

Language: Английский

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Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

Annals of Oncology, Journal Year: 2022, Volume and Issue: 34(1), P. 10 - 32

Published: Oct. 25, 2022

Language: Английский

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Clinical management of metastatic colorectal cancer in the era of precision medicine

CA A Cancer Journal for Clinicians, Journal Year: 2022, Volume and Issue: 72(4), P. 372 - 401

Published: April 26, 2022

Colorectal cancer (CRC) represents approximately 10% of all cancers and is the second most common cause deaths. Initial clinical presentation as metastatic CRC (mCRC) occurs in 20% patients. Moreover, up to 50% patients with localized disease eventually develop metastases. Appropriate management these still a challenging medical issue. Major efforts have been made unveil molecular landscape mCRC. This has resulted identification several druggable tumor targets aim developing personalized treatments for each patient. review summarizes improvements mCRC emerging era precision medicine. In fact, stratification, on which current treatment algorithm based, although it does not completely represent complexity this disease, first significant step toward clinically informative genetic profiling implementing more effective therapeutic approaches. relevant increase control patient survival. The next steps will be integrate comprehensive knowledge gene alterations, microenvironment protein expression profiling, host immune competence well application resulting dynamic changes medicine-based continuum care approach could result individual prognostic predictive parameters, help clinician choosing appropriate program(s) throughout entire journey CA Cancer J Clin. 2022;72:000-000.

Language: Английский

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Treatment of Metastatic Colorectal Cancer: ASCO Guideline

Journal of Clinical Oncology, Journal Year: 2022, Volume and Issue: 41(3), P. 678 - 700

Published: Oct. 17, 2022

To develop recommendations for treatment of patients with metastatic colorectal cancer (mCRC).ASCO convened an Expert Panel to conduct a systematic review relevant studies and clinical practice.Five reviews 10 randomized controlled trials met the inclusion criteria.Doublet chemotherapy should be offered, or triplet therapy may offered previously untreated, initially unresectable mCRC, on basis included in combination anti-vascular endothelial growth factor antibodies. In first-line setting, pembrolizumab is recommended mCRC microsatellite instability-high deficient mismatch repair tumors; anti-epidermal receptor stable proficient left-sided treatment-naive RAS wild-type mCRC; right-sided mCRC. Encorafenib plus cetuximab treated BRAF V600E-mutant that has progressed after at least one previous line therapy. Cytoreductive surgery systemic selected peritoneal metastases; however, addition hyperthermic intraperitoneal not recommended. Stereotactic body radiation following oligometastases liver who are considered candidates resection. Selective internal routinely unilobar bilobar metastases liver. Perioperative alone potentially curative resection metastases. Multidisciplinary team management shared decision making Qualifying statements further details related implementation guideline also included.Additional information available www.asco.org/gastrointestinal-cancer-guidelines.

Language: Английский

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Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C

New England Journal of Medicine, Journal Year: 2022, Volume and Issue: 388(1), P. 44 - 54

Published: Dec. 21, 2022

Adagrasib, an oral small-molecule inhibitor of mutant KRAS G12C protein, has shown clinical activity in pretreated patients with several tumor types, including colorectal cancer. Preclinical studies suggest that combining a epidermal growth factor receptor antibody could be effective strategy.In this phase 1-2, open-label, nonrandomized trial, we assigned heavily metastatic cancer to receive adagrasib monotherapy (600 mg orally twice daily) or (at the same dose) combination intravenous cetuximab once week (with initial loading dose 400 per square meter body-surface area, followed by 250 meter) every 2 weeks 500 meter). The primary end points were objective response (complete partial response) and safety.As June 16, 2022, total 44 had received adagrasib, 32 therapy cetuximab, median follow-up 20.1 months 17.5 months, respectively. In group (43 evaluable patients), was reported 19% (95% confidence interval [CI], 8 33). duration 4.3 CI, 2.3 8.3), progression-free survival 5.6 4.1 8.3). combination-therapy (28 46% 28 66). 7.6 5.7 not estimable), 6.9 5.4 8.1). percentage grade 3 4 treatment-related adverse events 34% 16% group. No 5 observed.Adagrasib antitumor G12C, both as cetuximab. more than 6 Reversible common two groups. (Funded Mirati Therapeutics; KRYSTAL-1 ClinicalTrials.gov number, NCT03785249.).

Language: Английский

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Effective drug combinations in breast, colon and pancreatic cancer cells

Nature, Journal Year: 2022, Volume and Issue: 603(7899), P. 166 - 173

Published: Feb. 23, 2022

Abstract Combinations of anti-cancer drugs can overcome resistance and provide new treatments 1,2 . The number possible drug combinations vastly exceeds what could be tested clinically. Efforts to systematically identify active the tissues molecular contexts in which they are most effective accelerate development combination treatments. Here we evaluate potency efficacy 2,025 clinically relevant two-drug combinations, generating a dataset encompassing 125 molecularly characterized breast, colorectal pancreatic cancer cell lines. We show that synergy between is rare highly context-dependent, targeted agents likely synergistic. incorporate multi-omic features biomarkers specify synergistic their contexts, including basal-like breast cancer, microsatellite-stable or KRAS -mutant colon cancer. Our results irinotecan CHEK1 inhibition have effects – TP53 double-mutant cells, leading apoptosis suppression tumour xenograft growth. This study identifies distinct subpopulations resource guide rational efforts develop combinatorial

Language: Английский

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Rational combinations of targeted cancer therapies: background, advances and challenges

Nature Reviews Drug Discovery, Journal Year: 2022, Volume and Issue: 22(3), P. 213 - 234

Published: Dec. 12, 2022

Language: Английский

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Trifluridine–Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer

New England Journal of Medicine, Journal Year: 2023, Volume and Issue: 388(18), P. 1657 - 1667

Published: May 3, 2023

In a previous phase 3 trial, treatment with trifluridine-tipiracil (FTD-TPI) prolonged overall survival among patients metastatic colorectal cancer. Preliminary data from single-group and randomized 2 trials suggest that FTD-TPI in addition to bevacizumab has the potential extend survival.We randomly assigned, 1:1 ratio, adult who had received no more than two chemotherapy regimens for of advanced cancer receive plus (combination group) or alone (FTD-TPI group). The primary end point was survival. Secondary points were progression-free safety, including time worsening Eastern Cooperative Oncology Group (ECOG) performance-status score 0 1 (on scale 5, higher scores indicating greater disability).A total 246 assigned each group. median 10.8 months combination group 7.5 (hazard ratio death, 0.61; 95% confidence interval [CI], 0.49 0.77; P<0.001). 5.6 2.4 disease progression 0.44; CI, 0.36 0.54; most common adverse events both groups neutropenia, nausea, anemia. No treatment-related deaths reported. ECOG 9.3 6.3 0.43 0.67).Among refractory cancer, resulted longer alone. (Funded by Servier Taiho Oncology; SUNLIGHT ClinicalTrials.gov number, NCT04737187; EudraCT 2020-001976-14.).

Language: Английский

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Independent Drug Action in Combination Therapy: Implications for Precision Oncology

Cancer Discovery, Journal Year: 2022, Volume and Issue: 12(3), P. 606 - 624

Published: Jan. 4, 2022

Combination therapies are superior to monotherapy for many cancers. This advantage was historically ascribed the ability of combinations address tumor heterogeneity, but synergistic interaction is now a common explanation as well design criterion new combinations. We review evidence that independent drug action, described in 1961, explains efficacy practice-changing combination therapies: it provides populations patients with heterogeneous sensitivities multiple chances benefit from at least one drug. Understanding response heterogeneity could reveal predictive or pharmacodynamic biomarkers more precise use existing drugs and realize benefits additivity synergy.Significance:. The model action represents an effective means predict magnitude likely be observed clinical trials therapies. "bet-hedging" strategy implicit suggests individual often only subset—sometimes one—of combination. Personalized, targeted therapy, consisting agents active particular patient, will increase, perhaps substantially, therapeutic benefit. Precision approaches this type require better understanding variability biomarkers, which entail preclinical research on diverse panels cancer models rather than studying synergy unusually sensitive models.

Language: Английский

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Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C

New England Journal of Medicine, Journal Year: 2023, Volume and Issue: 389(23), P. 2125 - 2139

Published: Oct. 22, 2023

G12C is a mutation that occurs in approximately 3 to 4% of patients with metastatic colorectal cancer. Monotherapy KRAS inhibitors has yielded only modest efficacy. Combining the inhibitor sotorasib panitumumab, an epidermal growth factor receptor (EGFR) inhibitor, may be effective strategy.

Language: Английский

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