P-73 Clinical prognostic factors for overall survival and time to progression in RAS-wild type metastatic colorectal cancer treated with anti-EGFR monoclonal antibodies as third or subsequent-line therapy

Purpose Previously, we reported results of Intergroup N9741, which compared standard bolus fluorouracil (FU), leucovorin, plus irinotecan (IFL) with infused FU, leucovorin, plus oxaliplatin (FOLFOX4) and irinotecan plus oxaliplatin in patients with untreated metastatic colorectal cancer. High rates of grade ≥ 3 toxicity on IFL (resulting in some deaths) led us to reduce the starting doses of both irinotecan and FU by 20% (rIFL). This article compares rIFL with FOLFOX4. Patients and Methods The primary comparison was time to progression, with secondary end points of response rate (RR), overall survival, and toxicity. Results Three hundred five patients were randomly assigned. The North Central Cancer Treatment Group Data Safety Monitoring Committee interrupted enrollment at a planned interim analysis when outcomes crossed predetermined stopping boundaries. The results were significantly superior for FOLFOX4 compared with rIFL for time to progression (9.7 v 5.5 months, respectively; P < .0001), RR (48% v 32%, respectively; P = .006), and overall survival (19.0 v 16.3 months, respectively; P = .026). Toxicity profiles were not significantly different between regimens for nausea, vomiting, diarrhea, febrile neutropenia, dehydration, or 60-day all-cause mortality. Sensory neuropathy and neutropenia were significantly more common with FOLFOX4. Approximately 75% of patients in both arms received second-line therapy; 58% of rIFL patients received oxaliplatin-based second-line therapy, and 55% of FOLFOX4 patients received irinotecan-based regimens as second-line therapy. Conclusion FOLFOX4 led to superior RR, time to progression, and overall survival compared with rIFL. The survival benefit for FOLFOX4 observed in the earlier stage of the study was preserved with equal use of either irinotecan or oxaliplatin as second-line therapy.

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Molecular and clinical prognostic factors in metastatic colorectal cancer (CRC) patients (pts): A retrospective study.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.511 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 511-511

Author(s):

Luisa Foltran ◽

Paola Ermacora ◽

Nicoletta Pella ◽

Giuseppe Aprile ◽

Giovanna De Maglio ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Metastatic Colorectal Cancer ◽

Univariate Analysis ◽

University Hospital ◽

Braf V600e ◽

Molecular Profile ◽

Wild Type ◽

Clinical Variables

511 Background: Strong evidence is emerging about the usefulness of mutational profiling for CRC pts. This study aimed to evaluate the overall survival in three molecular groups, taking as reference the all-wild type category: (1) BRAF mutated; (2) KRAS mutated codons 12-13 only; (3) any of KRAS codons 61-146, PIK3CA exon 9-20 or NRAS cod 12-13-61 mutations. Also clinical variables were investigated as potential prognostic factors. Methods: Data of 194 consecutive pts treated for metastatic colorectal cancer (mCRC) at our University Hospital in Udine, Italy, between Jan 2004 and Jan 2013 were reviewed. Point mutations were detected by pyrosequencing platform PyroMark Q96 ID instrument for KRAS/NRAS codons 12, 13, 61, and 146, BRAF exon 15, and PIK3CA exons 9 and 20. Clinical and molecular prognostic factors were identified using the Cox proportional hazards model. Results: The all wild-type population consisted of 76 pts (39%). 62 cases (32%) harboured mutations in KRAS codons 12-13. BRAF V600E mutation was found in 10 (5.2%) samples. Mutations in KRAS 61-146, PIK3CA and NRAS codons were detected in 9 (4.6%), 32 (16.5%) and 6 (3.1%) pts, respectively. All factors significant in univariate analysis were subjected to multivariate analysis (see Table). The all-wild type category had the longest survival (27.7 months). Patients carrying BRAF mutations reported an overall survival of 7.6 months and those with KRAS 12-13 mutation 16.7 months. Conclusions: This study reinforces the prognostic value of a full mutational molecular profile and points out some prognostic clinical factors in CRC. The influence of clinical variables such as right colon cancer, primary tumour not resected, exposure to bevacizumab and lines of chemotherapy need further investigation. [Table: see text]

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Faculty Opinions recommendation of Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727734555.793550882 ◽

2018 ◽

Author(s):

Sebastian Stintzing

Keyword(s):

Colorectal Cancer ◽

Clinical Trial ◽

Overall Survival ◽

Metastatic Colorectal Cancer ◽

Randomized Clinical Trial ◽

Wild Type ◽

First Line ◽

Line Chemotherapy

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Efficacy of CapeOX plus Cetuximab Treatment as a First-Line Therapy for Patients with Extended RAS/BRAF/PIK3CA Wild-Type Advanced or Metastatic Colorectal Cancer

Journal of Cancer ◽

10.7150/jca.26840 ◽

2018 ◽

Vol 9 (22) ◽

pp. 4092-4098

Author(s):

Shigeyoshi Iwamoto ◽

Hiromichi Maeda ◽

Shoichi Hazama ◽

Koji Oba ◽

Naoko Okayama ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Wild Type ◽

First Line ◽

First Line Therapy ◽

Line Therapy

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Impact of delayed addition of anti-EGFR monoclonal antibodies on the outcome of first-line therapy in metastatic colorectal cancer patients: A retrospective registry-based analysis

Annals of Oncology ◽

10.1093/annonc/mdy281.038 ◽

2018 ◽

Vol 29 ◽

pp. viii165

Author(s):

T. Buchler ◽

O. Fiala ◽

V. Veskrnova ◽

R. Chloupkova ◽

A. Poprach ◽

...

Keyword(s):

Colorectal Cancer ◽

Monoclonal Antibodies ◽

Metastatic Colorectal Cancer ◽

Cancer Patients ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Colorectal Cancer Patients

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Weekly Irinotecan in Patients with Metastatic Colorectal Cancer Failing 5-Fluorouracil-Based Chemotherapy: Efficacy and Prognostic Factors

Tumori Journal ◽

10.1177/030089160308900207 ◽

2003 ◽

Vol 89 (2) ◽

pp. 141-145 ◽

Cited By ~ 3

Author(s):

Aziz Karaoğrlu ◽

Suayib Yalcin ◽

Gülten Tekuzman ◽

Ayse Kars ◽

Ismail Çelik ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Objective Response ◽

Response Duration ◽

Response To Treatment ◽

Time To Progression ◽

Median Response ◽

Poor Prognostic Factor ◽

Histologic Subtype

Aims and background We evaluated the efficacy and tolerability of weekly irinotecan as a second-line treatment in patients with colorectal cancer failing 5-fluorouracil-based chemotherapy and searched for predictive and prognostic factors. Methods A total of 36 patients were included. Median age was 53 years (range, 33-72). One treatment cycle consisted of irinotecan, 100 mg/m2 weekly, for 4 weeks followed by a 2-week rest. Gender, age, primary site, number of metastatic sites, histologic subtype, differentiation, pretreatment CEA, CA 19-9 and lactate dehydrogenase levels and marker response to treatment were investigated as predictive factors for response to treatment and as prognostic factors in the overall survival and time to progression of the patients. Results A total of 120 cycles (median, 3 cycles) was delivered. An overall 14% objective response rate (1 complete and 4 partial responses) was achieved. The median response duration was 4 months (range, 2-7). Another 36% of the patients had stable disease for a median duration of 4 months (range, 2-8). Median time-to-disease progression was 4 months and overall median survival was 12 months (95% confidence interval, 9-15). Pretreatment serum CA 19-9 level and marker response to two courses of treatment were found to be clinically significant in time to progression and overall survival. Younger age (≤45 years) was a poor prognostic factor associated with a shorter time to progression. The major toxicity was grade 3-4 diarrhea, which occurred in 28% of the patients, and treatment was discontinued in 3 (8%) patients due to toxicity. Other hematological and non-hematological toxicities were mild and manageable. Conclusions We concluded that weekly irinotecan at the dose of 100 mg/m2 is an effective and tolerable treatment option, with a 50% disease control rate, for patients with colorectal cancer failing previous 5-fluorouracil-based chemotherapy.

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