Treatment of Patients With Metastatic Colorectal Cancer in a Real-World Scenario: Probability of Receiving Second and Further Lines of Therapy and Description of Clinical Benefit

Tampellini, Marco; Maïo, Massimo Di; Baratelli, Chiara; Anania, Lorenzo; Brizzi, Maria Pia; Sonetto, Cristina; Salvia, Anna La; Scagliotti, Giorgio Vittorio

doi:10.1016/j.clcc.2017.03.019

Cited by 24 publications

(22 citation statements)

References 15 publications

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“…This result essentially coincides with those of Ruff et al who found an increase in the toxicity profile of individuals aged more than 65 years in an age-based analysis of the VELOUR trial [11]. This group continues to be more complex in second-line treatment for mCRC [13]. Therefore, much remains to be done in this field.…”

Section: Discussionsupporting

confidence: 87%

“…All these data indicate that in the real world, where patients are often older, have comorbidities, and worse functional status, the risk-benefit balance could differ from that initially expected [13]. Our group posed the working hypothesis that actual efficacy and safety outcomes might differ from the VELOUR study results, particularly bearing in mind that modified FOLFIRI regimens are commonly used with the aim of decreasing toxicity in vulnerable patients [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

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Prognostic Nomogram and Patterns of Use of FOLFIRI-Aflibercept in Advanced Colorectal Cancer: A Real-World Data Analysis

et al. 2019

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Introduction The VELOUR study evaluated the efficacy and safety of adding aflibercept to FOLFIRI (fluorouracil, leucovorin, irinotecan) in second‐line therapy for metastatic colorectal cancer (mCRC). However, a nomogram that can stratify patients according to prognosis is unavailable, and the frequency and effect of the pragmatic use of modified schedules in actual practice remains unknown. Method The sample consists of 250 patients with mCRC treated with aflibercept and irinotecan‐based chemotherapy at nine Spanish academic centers between January 2013 and September 2015. The result of a Cox proportional hazards model regression for overall survival (OS), adjusted for covariates available in daily practice, was represented as a nomogram and web‐based calculator. Harrell's c‐index was used to assess discrimination. Results The prognostic nomogram for OS includes six variables: Eastern Cooperative Oncology Group performance status, tumor location, number of metastatic sites, mutational status, better response to previous treatment(s), and carcinoembryonic antigen. The model is well calibrated and has acceptable discriminatory capacity (optimism‐corrected c‐index, 0.723; 95% confidence interval [CI], 0.666–0.778). Median OS was 6.1 months (95% CI, 5.1–8.8), 12.4 months (95% CI, 9.36–14.8), and 22.9 months (95% CI, 16.6–not reached) for high‐, intermediate‐, and low‐risk groups, respectively. Age, comorbidity, or use of modified FOLFIRI regimens did not affect prognosis in this series. Grade 3–4 adverse events were less common following modified schedules. The admission rate because of toxicity was higher in ≥65 years (9.7% vs. 19.6%; odds ratio, 2.26; p = .029). Conclusion We have developed and internally validated a prognostic model for use in individuals with colorectal cancer initiating therapy with FOLFIRI‐aflibercept to predict both OS and the effect of pragmatic modifications of the classic regime on efficacy and safety. This can aid in decision making and in designing future trials. Implications for Practice In this study, the authors developed and conducted the internal validation of a prognostic nomogram that makes it possible to stratify patients who are eligible for second‐line FOLFIRI‐aflibercept based on their probability of survival. This model was developed in a multicenter sample from nine Spanish hospitals. Furthermore, to increase the study's validity, the practical use of aflibercept in this setting was investigated, including doses or pragmatic modifications. The results suggest that the modified schedules often used in this daily clinical practice‐based patient population are associated with less severe toxicity without apparent detriment to survival endpoints. It is believed that these data complement the information provided by the VELOUR trial and are relevant for the oncologist in treating colon cancer in the second‐line setting.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Prognostic Nomogram and Patterns of Use of FOLFIRI-Aflibercept in Advanced Colorectal Cancer: A Real-World Data Analysis

et al. 2019

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“…The expert panel recognized that many US clinicians use regorafenib following chemotherapy reintroduction; however, there is little evidence to support this strategy. 2 Indeed, no randomized study has addressed this question to date. Furthermore, the response to chemotherapy reintroduction can vary widely based on previous response to chemotherapy and the time since the prior treatment.…”

Section: Treatment Sequencingmentioning

confidence: 99%

“…Overall survival (OS) in patients with metastatic colorectal cancer (mCRC) has been improving over the past 2 decades, and the median has now reached more than 30 months. [1][2][3][4] This increase has been driven by several factors, including improvements to first-line treatments and their strategic use, and an increase in available options. [2][3][4] First-line and second-line treatment options for patients with mCRC include doublet or triplet chemotherapy plus a targeted biologic, such as an anti-angiogenic or, in patients with RAS wild-type (WT) disease, an epidermal growth factor receptor (EGFR) inhibitor.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4] This increase has been driven by several factors, including improvements to first-line treatments and their strategic use, and an increase in available options. [2][3][4] First-line and second-line treatment options for patients with mCRC include doublet or triplet chemotherapy plus a targeted biologic, such as an anti-angiogenic or, in patients with RAS wild-type (WT) disease, an epidermal growth factor receptor (EGFR) inhibitor. [4][5][6] In the third-line and later-line setting, regorafenib and trifluridine/tipiracil are available for patients with mCRC [4][5][6] whose disease has progressed despite treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (anti-VEGF) therapy and, if RAS WT, an anti-EGFR therapy, or who have contraindications to these treatments 7,8 (Table 1 and Table 2).…”

Section: Introductionmentioning

confidence: 99%

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Third- or Later-line Therapy for Metastatic Colorectal Cancer: Reviewing Best Practice

Bekaii‐Saab

Kim

et al. 2019

Clinical Colorectal Cancer

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An increasing number of patients with metastatic colorectal cancer (mCRC) are able to receive 3 or more lines of therapy. Treatments in this setting can include regorafenib (an oral multikinase inhibitor), trifluridine/tipiracil hydrochloride (TAS-102), antibodies that target epidermal growth factor receptor for patients with RAS wild-type tumors (if no prior exposure), and, where approved, anti-programmed cell death protein 1 inhibitors for patients with microsatellite instability-high mCRC. Although guidelines describe the available treatment options, few insights are provided to guide selection and sequencing. In this article, we share expert opinion from diverse geographic regions, to offer guidance for best practice when selecting and managing third-line treatment for mCRC. Various factors, including performance status, age, and tumor sidedness, can be used to guide treatment selection. Biomarkers, such as RAS, BRAF, and microsatellite instability, can be useful for treatment stratification. Management of adverse events, to maintain quality of life, is a key consideration and is crucial to best practice in this setting. Common toxicities associated with third-line treatments are hand-foot skin reaction, fatigue, diarrhea, and cytopenias. Patients who receive third-line and later-line treatments should be monitored for these events, especially during the first 2 cycles. Dose modifications can also be used to manage toxicities and to minimize the effect on quality of life, while maximizing treatment benefit. Clinical trials of emerging agents, new treatment combinations, and novel therapies continue the efforts to improve outcomes for patients with mCRC. Sharing expert opinions on best practice for treatment selection and management can ultimately improve outcomes for patients with mCRC.

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Anti-EGFR Rechallenge in Patients With Refractory ctDNA RAS/BRAF wt Metastatic Colorectal Cancer

Ciardiello,

Martinelli,

Troiani

et al. 2024

JAMA Netw Open

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ImportanceThe available evidence regarding anti–epidermal growth factor receptor (EGFR) inhibitor rechallenge in patients with refractory circulating tumor DNA (ctDNA) RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) is derived from small retrospective and prospective studies.ObjectiveTo evaluate the efficacy of anti-EGFR rechallenge in patients with refractory ctDNA RAS/BRAF wt mCRC.Design, Setting, and ParticipantsThis nonrandomized controlled trial used a pooled analysis of individual patient data from patients with RAS/BRAF wt ctDNA mCRC enrolled in 4 Italian trials (CAVE, VELO, CRICKET, and CHRONOS) and treated with anti-EGFR rechallenge between 2015 and 2022 (median [IQR] follow-up, 28.1 [25.8-35.0] months).InterventionPatients received anti-EGFR rechallenge therapy, including cetuximab plus avelumab, trifluridine-tipiracil plus panitumumab, irinotecan plus cetuximab, or panitumumab monotherapy.Main Outcomes and MeasuresOverall survival (OS), progression-free survival (PFS), overall response rate (ORR), and disease control rate (DCR) were calculated. Exploratory subgroup analysis evaluating several clinical variables was performed. Safety was reported.ResultsOverall, 114 patients with RAS/BRAF wt ctDNA mCRC (median [IQR] age, 61 [29-88] years; 66 men [57.9%]) who received anti-EGFR rechallenge as experimental therapy (48 received cetuximab plus avelumab, 26 received trifluridine-tipiracil plus panitumumab, 13 received irinotecan plus cetuximab, and 27 received panitumumab monotherapy) were included in the current analysis. Eighty-three patients (72.8%) had received 2 previous lines of therapy, and 31 patients (27.2%) had received 3 or more previous lines of therapy. The ORR was 17.5% (20 patients), and the DCR was 72.3% (82 patients). The median PFS was 4.0 months (95% CI, 3.2-4.7 months), and the median OS was 13.1 months (95% CI, 9.5-16.7 months). The subgroup of patients without liver involvement had better clinical outcomes. The median PFS was 5.7 months (95% CI, 4.8-6.7 months) in patients without liver metastasis compared with 3.6 months (95% CI, 3.3-3.9 months) in patients with liver metastasis (hazard ratio, 0.56; 95% CI, 0.37-0.83; P = .004). The median OS was 17.7 months (95% CI, 13-22.4 months) in patients without liver metastasis compared with 11.5 months (95% CI, 9.3-13.9 months) in patients with liver metastasis (hazard ratio, 0.63; 95% CI, 0.41-0.97; P = .04). Treatments showed manageable toxic effects.Conclusions and RelevanceThese findings suggest that anti-EGFR rechallenge therapy has promising antitumor activity in patients with refractory ctDNA RAS/BRAF wt mCRC. Within the limitation of a subgroup analysis, the absence of liver metastases was associated with significant improved survival.Trial RegistrationClinicalTrials.gov Identifiers: NCT02296203; NCT04561336; NCT03227926; NCT05468892

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Treatment of Patients With Metastatic Colorectal Cancer in a Real-World Scenario: Probability of Receiving Second and Further Lines of Therapy and Description of Clinical Benefit

Abstract: Our study demonstrated that of 4 patients submitted to a 1L, about 3 will receive a 2L, about 2 a 3L, and nearly 1 a 4L. Later lines could be beneficial even though earlier ones were not.

Cited by 24 publications

References 15 publications

Prognostic Nomogram and Patterns of Use of FOLFIRI-Aflibercept in Advanced Colorectal Cancer: A Real-World Data Analysis

Prognostic Nomogram and Patterns of Use of FOLFIRI-Aflibercept in Advanced Colorectal Cancer: A Real-World Data Analysis

Third- or Later-line Therapy for Metastatic Colorectal Cancer: Reviewing Best Practice

Anti-EGFR Rechallenge in Patients With Refractory ctDNA RAS/BRAF wt Metastatic Colorectal Cancer

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