Choice of sequential biologic therapies in metastatic colorectal cancer (mCRC): A cost comparison analysis for wild-type KRAS mCRC patient population in Brazil.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14679-e14679
Author(s):  
Rui Weschenfelder ◽  
Caio Timko Buschinelli
Keyword(s):  
Colorectal Cancer ◽  
Treatment Options ◽  
Drug Acquisition ◽  
Cost Savings ◽  
Cost Comparison ◽  
Wild Type ◽  
Payer Perspective ◽  
Third Line ◽  
Cost Comparison Analysis ◽  
Entire Treatment

e14679 Background: Colorectal cancer is the third most common cancer and the second leading cause of cancer-related death in Brazil. Metastatic disease affects up to 50% of patients resulting in 5-year survival of less than 10%. Therefore, there is an increasing interest about the best treatment options, mainly regarding biologics and their sequencing across first line (1L) and second line (2L) treatment of mCRC. Modern series show that the probability of a patient receives 1L, 2L and a third line (3L) therapy is approximately 99%, 70% and 40%, respectively. In addition, in 2012, the ML 18147 study demonstrated the benefit of sequential use, 1L and 2L, of bevacizumab (bev) based combination in mCRC and considering this emerging data, it is important to understand the implications in terms of costs for the Brazilian private healthcare system. Methods: A costing tool was developed to compare the sequencing costs of 1L → 2L regimens used for treatment of wild-type KRAS mCRC patients. Dosing schedules were derived from labels, clinical trials and expert opinion. Analysis was performed from a private payer perspective and included drug-acquisition and administration costs only. Sequences in the ML18147 study (1L bev 5mg/kg+FOLFOX → 2L bev 5mg/kg+FOLFIRI and 1L bev 5mg/kg+FOLFIRI→2L bev 5mg/kg+FOLFOX) were compared to another frequently used sequence in Brazil where bev is replaced by cetuximab(cet) in 1L (1L cet 400-250mg/m2+ FOLFIRI → 2L bev 5 mg/Kg + FOLFOX). Results: Average costs per patient per month were Brz 21,285.50 for sequences with bev in 1L and 2L and Brz 24,191.68 when bev is replaced by cet in 1L. The average cost savings per patient for the entire treatment were Brz 28,767 (1L bev 5mg/kg + FOLFOX → 2L bev 5mg/kg + FOLFIRI vs 1L cet + FOLFIRI → 2L bev + FOLFOX) and Brz 29,938 (1L bev 5mg/kg + FOLFIRI → 2L bev 5mg/kg + FOLFOX vs1L cet + FOLFIRI → 2L bev + FOLFOX). Conclusions: Sequential use of bev in 1L and 2L mCRC according to the ML18147 study protocol is less costly compared to another sequence of biologics that starts with cet in 1L followed by bev in 2L. Resources savings with sequential bev have the potential to optimize 3L treatment strategy for wild-type kras mCRC patients in Brazil.

scholarly journals Practical considerations in the use of regorafenib in metastatic colorectal cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592095686
Author(s):  
Fotios Loupakis ◽  
Lorenzo Antonuzzo ◽  
Jean-Baptiste Bachet ◽  
Feng-Che Kuan ◽  
Teresa Macarulla ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Decision Making ◽  
Metastatic Colorectal Cancer ◽  
Treatment Options ◽  
Daily Practice ◽  
The Third ◽  
Appropriate Treatment ◽  
Third Line ◽  
Line Setting ◽  
Physician Patient

Over the past 20 years, management of patients with metastatic colorectal cancer (mCRC) has improved considerably, leading to increased overall survival and more patients eligible for third- or later-line therapy. Currently, two oral therapies are recommended in the third-line treatment of mCRC, regorafenib and trifluridine/tipiracil. Selecting the most appropriate treatment in the third-line setting poses different challenges compared with treatment selection at earlier stages. Therefore, it is important for physicians to understand and differentiate between available treatment options and to communicate the benefits and challenges of these to patients. In this narrative review, practical information on regorafenib is provided to aid physicians in their decision-making and patient communications in daily practice. We discuss the importance of appropriate patient selection and adverse events management through close patient monitoring and dose adjustments to ensure patients stay on treatment for longer and receive as much benefit as possible. We also highlight key physician–patient communication points to facilitate shared decision-making.

Clinical benefit rate (CBR) of panitumumab monotherapy among patients with KRAS wild-type metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14176-e14176
Author(s):  
Hagen F. Kennecke ◽  
Howard John Lim ◽  
Balvindar Singh Johal ◽  
Muhammad Zulfiqar ◽  
Caroline Speers
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Primary Endpoint ◽  
Clinical Benefit ◽  
Single Agent ◽  
Wild Type ◽  
Clinical Benefit Rate ◽  
Previous Therapy ◽  
Study Results ◽  
Third Line

e14176 Background: Panitumumab (Pmab) improves progression free survival as first-, second- and third-line therapy for KRAS wild-type (wt) metastatic colorectal cancer (mCRC). Only in the third-line setting is there evidence of benefit of Pmab monotherapy. In this analysis of an exploratory biomarker study of Pmab monotherapy, the clinical benefit rate of Pmab according to previous lines of therapy is described. Methods: Patients (pts) with KRAS non-mutated, measurable MCRC previously treated with or ineligible for oxaliplatin/5-FU and irinotecan were treated with Pmab 6mg/kg IV q2w until progression or toxicity. The primary endpoint is clinical benefit rate (complete (CR) or partial response (PR) + prolonged stable disease (PSD) > = 24 weeks) by RECIST criteria. Results: The study completed accrual and (40) evaluable patients were treated between September 2009 and December 2011 of which 32 were evaluable for the primary endpoint. Median follow-up was 8.8 months, median age was 64.5 years and 90% were ECOG 0/1. Previous therapy was: 5-FU/Capecitabine(C) only in 12 pts, Irinotecan/5-FU/C only in 2 patients, Oxaliplatin/5-FU/C only in 3 pts, Oxaliplatin/Irinotecan/5-FU/C in 23 pts. 22 patients received prior Bevacizumab. Median number of cycles was 8 and 6 pts required a dose modification. There were 7 (22%) PRs and 7 (22%) pts experienced PSD >=24 weeks. Clinical benefit rate (PR+PSD) according to previous therapy was 33% (3/9) for 5FU/C only, 100% (2/2) Oxaliplatin/FU/C only, 0% (0/2) Irinotecan/FU/C only, and 47% (9/19) for Oxaliplatin/Irinotecan/5FU/C. Conclusions: Pmab monotherapy is well tolerated and response rates vary according to previous lines of therapy. Patients ineligible for irinotecan and/or oxaliplatin experience a high clinical benefit rate with single agent Panitumumab and should be considered for such therapy. Updated study results will be presented.

Hsa-miR-31-3p expression in FFPE tumor samples as a predictor of anti-EGFR response in patients with metastatic colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3562-3562 ◽  
Author(s):  
Gilles Manceau ◽  
Jean-Baptiste Bachet ◽  
Benoist Chibaudel ◽  
Francois Liebaert ◽  
Raphaële Thiébaut ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cox Proportional Hazards Model ◽  
Expression Level ◽  
Prognostic Impact ◽  
Wild Type ◽  
Training Set ◽  
Ffpe Samples ◽  
Validation Set ◽  
Third Line

3562 Background: In metastatic colorectal cancer (mCRC), KRAS mutations are associated with resistance to anti-EGFR antibodies. To identify, in wild-type KRAS mCRC patients, markers that predict response to anti-EGFR antibodies, we focused on miRNAs. Methods: Expression profile of 1145 miRNAs was done on 84 colorectal tumors and 5 normal colon mucosae. Correlations between miRNAs expression level and survival were based on frozen samples of a training set from a retrospective series of 33 patients treated by cetuximab and irinotecan and of two validation set from prospective collections of 38 patients treated by cetuximab or panitumumab based chemotherapy or by panitumumab and irinotecan as third-line, using an adjusted Cox proportional hazards model. Validation on FFPE samples was done on 39 patients treated with panitumumab and irinotecan as third-line. Results: A predictive signature of 11 miRNA linked to the PFS was identified (p<0.01) but only one, hsa-miR-31-3p, exhibited significant different expression level between tumor from bad prognosis and good prognosis from the training set. We tested expression of this miRNA on the training set, and found a HR of 1.9 CI95% [1.1-2.9]. In validation set, the prognostic impact of hsa-miR-31-3p the HR was estimated to 1.9 CI95% [1.1-3.1]. Using multivariate model obtained from the training set to the two validation set, we predict the PFS of the patients (accuracy of prediction: AUC = 0.77). We classified the validation set according to a free PFS score (P=0.005) with a specificity of 62% CI95% [38%-82%] and a sensitivity of 82% CI95% [56%-96%] for the prediction model. A nomogram, established taking into account hsa-miR-31-3p expression level, predicted the progression risk (P<0.0001). Confirmation of the predictive value of hsa-miR-31-3p expression on survival risk progression was done on FFPE sample (p=0.0006). Conclusions: This is the first tool to select individual patients with a wild-type KRAS tumor for anti-EGFR therapy from frozen or FFPE samples.

scholarly journals Phase II trial of biweekly cetuximab and irinotecan as third‐line therapy for pretreated KRAS exon 2 wild‐type colorectal cancer

2018 ◽  
Vol 109 (8) ◽  
pp. 2567-2575 ◽  
Author(s):  
Hiroki Osumi ◽  
Eiji Shinozaki ◽  
Tetsuo Mashima ◽  
Takeru Wakatsuki ◽  
Mitsukuni Suenaga ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Wild Type ◽  
Exon 2 ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line ◽  
Kras Exon

A single-arm trial of panitumumab in cetuximab refractory KRAS wild-type colorectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 428-428 ◽  
Author(s):  
R. C. Wadlow ◽  
A. F. Hezel ◽  
B. M. Wolpin ◽  
J. N. Allen ◽  
L. S. Blaszkowsky ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Type I Error ◽  
Human Monoclonal Antibody ◽  
Growth Factor Receptor ◽  
Chimeric Antibody ◽  
Type I ◽  
Wild Type ◽  
Third Line ◽  
Line Setting

428 Background: While FOLFOX or FOLFIRI with bevacizumab are the standard first-line regimens in the treatment of metastatic colorectal cancer, a role for epidermal growth factor receptor inhibitiion in KRAS wild-type colorectal cancer has been established in the second and third line setting. Cetuximab is a chimeric antibody that consists of approximately 30% murine protein, and panitumumab is a fully human monoclonal antibody. Correspondingly, the rates of severe hypersensitivity reactions are somewhat increased with cetuximab (3%) compared to panitumumab (1%). Presently, cetuximab is typically used in combination with irinotecan in the second or third line setting, and panitumumab is occasionally substituted if hypersensitivity occurs. The value of panitumumab as a salvage agent in cetuximab-resistant colorectal cancer is unknown. Methods: Panitumumab (6 mg/kg every 14 days) was administered to patients with KRAS wild-type metastatic colorectal cancer that had progressed on prior cetuximab. Treatment was continued until disease progression, death, inability to tolerate panitumumab, or study withdrawal. The primary endpoint was response rate (RR). Twenty patients were enrolled in the first stage and, if at least one responded, 12 additional patients were to be enrolled in a second stage. This two-stage design tested the null hypothesis that the RR is less than or equal to 1% versus greater than or equal to 10% with a type I error of 3.6% and 80% power. Blood samples were collected at baseline and prior to cycles 2 and 3 to evaluate for the presence of anti-cetuximab and anti-panitumumab antibodies using the Biacore immunoassay. Results: 22 patients with ECOG PS 0-2 were treated for a median of two cycles. The best response was stable disease (45%) and the RR was 0%. There were a total of 266 toxicities reported, the majority of which were mild (n = 184, 69%) or moderate (n = 63, 24%) in severity. There were 19 grade 3 and 0 grade 4 toxicities. Median overall survival was 1.9 months. Immunologic data will be reported at the time of presentation. Conclusions: Panitumumab is not active as salvage therapy for patients with cetuximab-resistant, KRAS wild-type metastatic colorectal cancer. [Table: see text]

Use and findings of K-ras in colorectal cancer (CRC) testing in administrative and electronic medical records (EMR) data from 2005 through 2010.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14146-e14146
Author(s):  
Satish Valluri ◽  
Sean D Sullivan ◽  
Scott David Ramsey ◽  
Charles Kreilick ◽  
Susan H Foltz Boklage ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Decision Making ◽  
Stage Iv ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Number Of Patients ◽  
Third Line ◽  
Line Of Therapy ◽  
The Impact

e14146 Background: The use of K-ras testing in clinical decision-making has grown over the past few years. The objective of this study was to evaluate, in a real world context, the trends and diagnostic findings of K-ras testing using managed care and EMR data. Methods: The Georgia Cancer Specialists Database EMR (2005-2010) and administrative data from the MarketScan and IMPACT database(s) was used to select patients with newly diagnosed colorectal cancer (CRC). We looked for trends in use of K-ras in relation to timing of chemotherapy administration. The EMR data provided information on k-ras mutation type. Results: In MarketScan, of the 23,548 patients with a diagnosis of CRC, 1,730 (7.3%) patients had a test ordered for K-ras between 2005 and 2010. The number of patients receiving K-ras increased with line of therapy: first line 336 patients (8.2%) of 4,098 treated, second line 455 patients (15.2%) of 2,984 treated, and third line 529 patients (33%) of 1,603 treated. We found similar results using the IMPACT database: 2,256 (7.8%) CRC patients had a test ordered for K-ras between 2005 and 2010. K-ras testing increased with line of therapy: first line 244 patients (7.8%), second line 510 (14.6%), and third line 650 patients (33.1%). EMR lab results from stage IV disease (n=349) consisted of 15% mutated type, 60% unknown and 25% wild type. For confirmed test results wild type represented 62.5% and mutated type 37.5%. Conclusions: Over the last six years, use of K-ras testing has increased in use in patients with CRC. The increase has occurred in later lines of therapy. The timing occurring late in therapy may limit the use of agents specific for this test.

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