Vectibix® is indicated for the treatment of patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC):Read More
Anti-EGFR plus chemotherapy is part of certain 1L targeted treatment recommendations for left-sided mCRC from the National Comprehensive Cancer Network® (NCCN®) and ASCO4,5
NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
*Patients with BRAF mutations other than V600E may be candidates for anti-EGFR therapy.4
In a real-world study, improved median overall survival was observed with 1L anti-EGFR therapy in patients with WT RAS and WT BRAF, left-sided mCRC.6
1L = first line; 5-FU = 5-fluorouracil; EGFR = epidermal growth factor receptor; ICD = International Classification of Diseases; mCRC = metastatic colorectal cancer; VEGF = vascular endothelial growth factor; WT = wild type.
Based on a retrospective review of patient data from the nationwide Flatiron Health database of de-identified electronic health records covering approximately 800 sites of care at ~280 US cancer clinics. Included patients were diagnosed with mCRC between January 2013 and December 2018 and received a standard first-line chemotherapy doublet defined as 5-FU/oxaliplatin (FOLFOX), capecitabine/oxaliplatin (CAPEOX), or 5-FU/irinotecan (FOLFIRI). Within this group, only patients who were documented as having RAS/RAF WT mCRC with a left-sided primary tumor (LSPT) as determined by ICD coding were included in the final analysis. LSPT defined as those located in the splenic flexure, descending, sigmoid, and rectum. Targeted therapy included anti-VEGF (bevacizumab) and anti-EGFR agents (cetuximab or panitumumab), which was considered part of first-line therapy if it was added within 2 months of the first administered dose of chemotherapy. Of 20,333 patients with mCRC included in the EHR-derived dataset, 9,753 received a standard chemotherapy doublet with or without targeted therapy. A tumor sidedness–specific ICD code was entered for 2,449 patients, with 1,607 documented as having an LSPT. Within the cohort, 456 patients received first-line chemotherapy alone, 965 received chemotherapy plus bevacizumab, and 186 received chemotherapy plus an anti-EGFR agent. When stratified by first-line therapy received, groups were balanced with regard to race, gender, performance status, disease presentation (recurrent vs de novo metastatic disease), and documented location of primary tumor.6
*44% RAS WT + 9% BRAF + 5% MSI + 5% HER2-amplified = 63%.
†Percentages are approximations. Overlapping aberrations may be observed in some tumors.
‡BRAF V600E mutation.3
BRAF = v‑raf murine sarcoma viral oncogene homolog B1; HER2 = human epidermal growth factor receptor 2; KRAS = Kristen rat sarcoma viral oncogene homolog; mCRC = metastatic colorectal cancer; MSI-H = microsatellite instability-high; MSI-H = microsatellite instability-low; MSS = microsatellite stable; MT = mutant type; NRAS = neuroblastoma rat sarcoma viral oncogene homolog; NTRK = neurotrophic tyrosine receptor kinase; RAS = rat sarcoma viral oncogene homolog; WT = wild‑type.
ASCO = American Society of Clinical Oncology; ESMO = European Society of Medical Oncology; MMR = mismatch repair; MSI = microsatellite instability.
Biomarker knowledge supports precise patient identification for 1L anti-EGFR targeted therapy3,8
Guideline Recommended: 100% of patients with mCRC tested for all relevant biomarkers9
N = 20,333
Based on a retrospective cohort study of patient data from the nationwide Flatiron Health database of de-identified electronic health records covering approximately 800 sites of care at ~280 US cancer clinics. All patients were aged 18 or older with de novo metastatic or a metastatic recurrence diagnosed with mCRC between January 1, 2013 and December 31, 2018. A patient was counted as “tested” if they underwent testing within 6 months of their diagnosis. A total of 20,333 patients were included in the analysis. Most patients (93.1%) were treated at community centers and 6.9% were treated at academic centers.9
MORE COMPREHENSIVE BIOMARKER TESTING HAS THE POTENTIAL TO OPTIMIZE TREATMENT & IMPROVE OUTCOMES
*Turnaround time is the time from which the sample arrives at the testing laboratory to when the oncologist/ordering physician receives the test results. ASCP/CAP/AMP/ASCO guidelines recommend a 10-working day turnaround time for the majority of tests.
1L = first line; CAP = College of American Pathologists; CRC = colorectal cancer; AMP = Association for Molecular Pathology: ASCO = American Society of Clinical Oncology: ASCP = American Society for Clinical Pathology; EGFR = epidermal growth factor receptor; HER2 = human epidermal growth factor receptor 2; mCRC = metastatic colorectal cancer; MMR = mismatch repair deficient; MSI = microsatellite instability; PCR = polymerase chain reaction; WT = wild type.
Identifying patients with WT RAS, WT BRAF, non-MSI-H, left-sided mCRC represents a paradigm shift to refine 1L targeted treatment selection2
TWO OUT OF THREE PATIENTS WITH mCRC HAVE LEFT-SIDED TUMORS13
ASCO GUIDELINES: SYSTEMIC THERAPY FOR mCRC ALGORITHM5
For full treatment guidelines see Morris VK, et al. J Clin Oncol. 2023;41:678-700.
*Defined as wild type in both KRAS and NRAS.13
†Decisions regarding treatment options and sequencing for all patients with mCRC should be made within the context of an MDT.
‡Doublet CT should be offered, or triplet CT may be offered. Shared decision-making is recommended, including a discussion of the potential for benefit and risk of harm; while survival and recurrence outcomes are improved, grade 3 or greater adverse events are more frequent with triplet CT compared to doublet CT.
§Anti-EGFR therapy is not recommended for patients with RAS-mutant mCRC.
**Anti-EGFR therapy is not recommended as a lone biologic agent for treatment-naïve patients with BRAF V600E-mutant mCRC.
††Although anti-EGFR therapy is preferred, anti-VEGF therapy remains an active treatment option for patients with left-sided treatment-naïve RAS wild-type mCRC.
This algorithm is derived from recommendations in Treatment of Metastatic Colorectal Cancer: ASCO Guideline. This is a tool based on an ASCO Guideline and is not intended to substitute for the independent professional judgment of the treating physician. Practice guidelines do not account for individual variation among patients. This tool does not purport to suggest any particular course of medical treatment. Use of the guideline and this tool are voluntary.
ASCO = American Society of Clinical Oncology; CT = chemotherapy; dMMR = deficient mismatch repair; doublet CT = FOLFOX, CAPOX, or FOLFIRI; EGFR = epidermal growth factor receptor; mCRC = metastatic colorectal cancer; MDT = multidisciplinary team; MSI = microsatellite instability; triplet CT = FOLFOXIRI; VEGF = vascular endothelial growth factor.
PARADIGM reinforces the value of:
LEARN HOW VECTIBIX® CLINICAL DATA HELPED EVOLVE BIOMARKER-BASED DECISIONS FOR PATIENTS WITH mCRC
Drs. Philip and Tauer are paid consultants for Amgen.
Dermatologic Toxicity: Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients receiving Vectibix® monotherapy [see Dosage and Administration (2.3), Warnings and Precautions (5.1), and Adverse Reactions (6.1)].
Please see Vectibix® full Prescribing Information, including Boxed WARNING.
Vectibix® is indicated for the treatment of patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC):
Vectibix® is not indicated for the treatment of patients with RAS-mutant mCRC or for whom RAS mutation status is unknown.
Dermatologic Toxicity: Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients receiving Vectibix® monotherapy [see Dosage and Administration (2.3), Warnings and Precautions (5.1), and Adverse Reactions (6.1)].
References 1. Morris VK, Kennedy EB, Baxter NN, et al. J Clin Oncol. 2023;41:678-700. 2. Doleschal B, Petzer A, Rumpold H. Front Oncol. 2022;12:1048166. 3. Cohen R, Pudlarz T, Delattre JF, Colle R, André T. Cancers (Basel). 2020;12:2350. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer V.4.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed August 7, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. 5. Systemic therapy for metastatic colorectal cancer (mCRC) algorithm. ASCO Guidelines®. 2022. 6. Nevala-Plagemann C, Iyengar S, Trunk AD, Pappas L, Haaland B, Garrido-Laguna I. J Natl Compr Canc Netw. 2022;20(3):268-275. 7. Sepulveda AR, Hamilton SR, Allegra CJ, et al. J Clin Oncol. 2017;35:1453-1486. 8. Cervantes A, Adam R, Roselló S, et al. Ann Oncol. 2023;34:10-32. 9. Iyer P, Deng M, Handorf EA, Nakhoda S, Dotan E. JNCI Cancer Spectr. 2022;6:pkac065. 10. Vectibix® (panitumumab) prescribing information, Amgen. 11. El-Deiry WS, Goldberg RM, Lenz HJ, et al. CA Cancer J Clin. 2019;69:305-343. 12. Pennell NA, Arcila ME, Gandara DR, West H. Am Soc Clin Oncol Educ Book. 2019;39:531-542. 13. Mendis S, Beck S, Lee B, et al. Asia Pac J Clin Oncol. 2019;15:136-143.