P-121 Efficacy and toxicity of biosimilar and original bevacizumab in the second-line treatment of metastatic colon cancer in routine clinical practice: Results of an observational multicenter study

e16161 Background: Docetaxel is standard of care for the treatment of HRPC, based on two large randomized clinical trials. The aim of this study was to determine if docetaxel use and effectiveness in routine clinical practice was similar to that seen in the TAX 327 randomized phase III clinical trial. Methods: A retrospective chart review was undertaken to assess patterns of docetaxel use for HRPC at our institution for the 2-year period since its approval for the first-line treatment of HRPC in 2005. Results: Eighty-eight patients, median age 71 and baseline PSA 107, received docetaxel in the first line setting. Main reasons for initiating docetaxel were rising PSA (90%) and progressive symptoms (71%). Eighteen percent of patients received docetaxel for rising PSA alone. A median of 7 cycles was administered. PSA response rates were 61%, time to response 1.5 months, and response duration 6.8 months. Disease progression was the most common reason for treatment discontinuation (36%). Main toxicities were fatigue (32%) and neuropathy (22%). Kaplan Meier survival analysis showed median duration of survival was 15.9 months (95% CI 12.4–20.5) from first drug use. 1-year survival was 0.63 (95% CI 0.52–0.72). Post-docetaxel, 36 patients received second-line treatment, mostly with mitoxantrone (89%). Second-line response rates were 22%, and median duration of response was 4 months. Conclusions: In routine clinical practice, docetaxel is a well-tolerated regimen for the treatment of HRPC. Response rates and toxicity profiles were comparable to the randomized trials. However, compared with the TAX 327 clinical trial, survival was slightly shorter than expected (15.9 vs. 18.9 months), possibly due to inclusion of patients with poorer performance status and comorbidities, who may be excluded from clinical trials. Second-line response rates were also comparable with previous reports. No significant financial relationships to disclose.

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Oxaliplatin and Fixed-Rate Infusional Gemcitabine in the Second-Line Treatment of Patients with Metastatic Colon Cancer: Final Results of a Phase II Trial Prematurely Closed as a Result of Poor Accrual

Clinical Colorectal Cancer ◽

10.3816/ccc.2007.n.032 ◽

2007 ◽

Vol 6 (9) ◽

pp. 641-645 ◽

Cited By ~ 6

Author(s):

Gilberto Lopes ◽

Jose Quesada ◽

Eugene Ahn ◽

Aurea Flores ◽

Afonso Ribeiro ◽

...

Keyword(s):

Colon Cancer ◽

Phase Ii ◽

Phase Ii Trial ◽

Metastatic Colon Cancer ◽

Line Treatment ◽

Second Line ◽

Fixed Rate

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Survival benefit associated with the number of chemotherapy/biologic treatment lines in 5,129 metastatic colon cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.559 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 559-559 ◽

Cited By ~ 1

Author(s):

Nader Hanna ◽

Corinne Woods ◽

Zhiyuan Zheng ◽

Ebere Onukwugha ◽

Brian S. Seal ◽

...

Keyword(s):

Colon Cancer ◽

Metastatic Colon Cancer ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Biologic Treatment ◽

Mortality Hazard ◽

Line Therapy ◽

Hazard Ratios ◽

First Line Treatment

559 Background: The purpose of this study was to investigate the association between multiple chemotherapy/biologic treatment lines and survival among patients diagnosed with metastatic colon cancer (mCC). Methods: Patients aged 66 to 105 years old diagnosed with mCC between 2003 and 2007 were selected for analysis from the Surveillance, Epidemiology and End Results SEER-Medicare data to determine the association between chemotherapy/biologic treatment lines and survival. We examined the survival benefits using Cox proportional-hazards regressions with inverse probability weighting method to adjust for the probability of receiving treatment lines. Results: Patients with no chemotherapy/biologic treatment had an adjusted median survival time of 6.8 months. Each chemotherapy/biologic treatment line received was associated with longer adjusted median survival times: 11.9 months, 23.2 months and 26.4 months for receipt of first-line treatment only, second-line treatment and subsequent treatment, respectively. Colon cancer-specific mortality hazard ratios (HRs) were 0.637, 0.391 and 0.350 (p<0.001 for each) for first-line, second-line and subsequent treatments, respectively. Overall mortality hazard ratios were 0.604, 0.398 and 0.364 (p<0.001 for each) for first-line, second-line and subsequent treatments, respectively. Compared to receiving only first-line treatment, proceeding to second-line treatment was associated with longer colon cancer-specific survival (HR=0.614, p<0.001) and longer overall survival (HR=0.659, p<0.001). Patients with a low-graded tumor had longer colon cancer-specific and overall survival (HR=0.746, p<0.001; HR=0.762, p<0.001, respectively) and lived 5.6 months longer. Factors associated with shorter survival were a higher age category and being female. Conclusions: Among mCC patients who survived at least 3 months from diagnosis, each chemotherapy/biologic treatment line was independently associated with significantly longer survival. Proceeding from first-line to second-line therapy or having a low-graded tumor was also associated with longer survival. Proceeding from second-line third-line therapy showed neither benefit nor harm.

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Efficacy of continuing anti-angiogenic agents in the second-line treatment for metastatic colon cancer depending on the KRAS mutation status: a meta-analysis

Colorectal Oncology ◽

10.17650/2220-3478-2018-8-2-38-45 ◽

2018 ◽

Vol 8 (2) ◽

pp. 38-45

Author(s):

M. Yu. Fedyanin ◽

A. A. Tryakin ◽

S. A. Tjulandin

Keyword(s):

Colon Cancer ◽

Overall Survival ◽

Meta Analysis ◽

Progression Free Survival ◽

Metastatic Colon Cancer ◽

Line Treatment ◽

Second Line ◽

Kras Gene ◽

Mutation Status ◽

Free Survival

Objective: to assess the efficacy of anti-angiogenic agents incorporated into second-line chemotherapeutic regimens for metastatic colon cancer depending on the KRAS gene mutation status.Materials and methods. We selected completed prospective randomized controlled phase III clinical trials evaluating the efficacy of antiangiogenic agents (bevacizumab, ramucirumab and aflibercept) added to second-line chemotherapy for metastatic colon cancer with subanalysis of treatment efficacy depending on the KRAS gene mutation status. Meta-analysis was performed using the ReviewManager (RevMan) v. 5.3 (The Cochrane Collaboration, Denmark).Results. Three studies (ML18147, RAISE, VELOUR) involving 2165 patients (1137 with KRAS wild-type tumors and 1028 with KRAS-mutant tumors) met the inclusion criteria and were included into this meta-analysis. The majority of patients (84 %) received bevacizumab in the first-line treatment. The results of our meta-analysis suggest that adding an anti-angiogenic drug to chemotherapy in patients with KRAS wildtype colon cancer significantly improved both progression-free survival (hazard ratio (HR) 0.71; 95 % confidence interval (CI) 0.62–0.80; р<0.00001; I2 = 22 %, p = 0.21) and overall survival (HR 0.76; 95 % CI 0.66–0.88; р= 0.0001; I2 = 0, p = 0.59). In patients with KRASmutant colon cancer, incorporation of an anti-angiogenic drug into the treatment regimen was not associated with better overall survival (ОР0.9; 95 % CI 0.79–1.03; р= 0.11; I2 = 0, p = 0.98), although improved progression-free survival (HR 0.78; 95 % CI 0.68–0.89; р= 0.0002; I2 = 0, p = 0.46). Conclusion. Continuation of anti-angiogenic therapy in the second-line treatment for metastatic colon cancer is most effective in patients with KRAS wild-type tumors. In individuals with KRAS-mutant tumors, continuation of bevacizumab or switch to another anti-angiogenic agent in the second-line treatment improves progression-free survival and has a statistically insignificant effect on overall survival.

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Does first-line treatment impact the cost-effectiveness of second-line treatment for elderly metastatic colon cancer patients?

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.585 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 585-585

Author(s):

C. Daniel Mullins ◽

Andinet Woldemichael ◽

Zhiyuan Zheng ◽

Ebere Onukwugha ◽

Brian S. Seal ◽

...

Keyword(s):

Colon Cancer ◽

Cost Effectiveness ◽

Real World ◽

Survival Benefit ◽

Metastatic Colon Cancer ◽

Line Treatment ◽

Second Line ◽

First Line ◽

The Real ◽

First Line Treatment

585 Background: Randomized clinical trials for second line treatment (Tx2) of metastatic colon cancer (mCC) often have strict inclusion/exclusion criteria regarding prior treatment, yet in the real world there is significant variation. This study aims to determine whether cost effectiveness estimates of Tx2 for elderly mCC patients varies by the regimen they received in first-line treatment (Tx1). Methods: We identified 3,211 elderly (age 66+) mCC patients in the SEER-Medicare dataset who received NCCN recommended Tx1 between 2003 and 2009. Patients were categorized by Tx1 based on a previously published algorithm as fluorouracil and leucovorin (5-FU/LV), irinotecan (IRI), oxaliplatin (OX), or “other,” which included IROX or biologics without OX or IRI. Separate 5-year incremental cost-effectiveness of Tx2 were calculated for each Tx1. Approximately 1% of patients with outlier costs were excluded. Patients enrolled in HMOs, lost Part A and/or B, and died of causes other than colon cancer are censored. We adjusted for censoring using the Inverse Probability Weighting (IPW) method. Costs were inflation-adjusted to 2009 dollars using the national monthly medical price index. Results: Among patients who received Tx1, 34% (n=1,090) received 5FU, 17% (n=530) received IRI, 46% (n=1,481) received OX, and 3% (n=110) received other (IROX or Biologics) regimens; 44.5% (n=1,440) proceeded to Tx2. Compared to those who do not receive Tx2, patients who received Tx2 following IROX or Biologics, IRI and 5FU in Tx1 live 292 (se = 4), 224 (se = 2), and 191 (se = 2) days longer and incur added costs of $49,096 (se = $7,137), $83,784 (se = $12,322), and $91,686 (se = $10,312), respectively. Recipients of OX in Tx1 did not receive a survival benefit from Tx2, despite additional costs of $46,849 (se = $10,468). Conclusions: The real-world survival benefit of Tx2 for elderly mCC patients in SEER-Medicare varied based on Tx1 from potential harm to a mean of 292 days of incremental survival. Similarly, the costs and cost effectiveness of Tx2 varied by Tx1. These results underscore the importance of considering prior treatment when evaluating the benefit of subsequent treatment for elderly mCC patients.

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The impact of comorbidity on costs and effects of second-line treatment among elderly metastatic colon cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.536 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 536-536

Author(s):

Andinet Woldemichael ◽

Ebere Onukwugha ◽

Zhiyuan Zheng ◽

Nader Hanna ◽

Brian S. Seal ◽

...

Keyword(s):

Colon Cancer ◽

Cost Effectiveness ◽

Incremental Cost ◽

Cancer Patients ◽

Metastatic Colon Cancer ◽

Line Treatment ◽

Second Line ◽

Elderly Age ◽

Co Morbidity ◽

The Impact

536 Background: The Charleston Co-morbidity Index (CCI) was developed as in hospital mortality indicatory and subsequently has been used to both predict and adjust survival differences in cancer patients. We therefore sought to examine how the incremental cost effectiveness of treating elderly metastatic colon cancer (mCC) patients with second-line treatment (Tx2) will vary based upon their baseline CCI. Methods: We identified 2,897 elderly (age 66+) mCC patients who received NCCN recommended first-line treatment (Tx1) between 2003 and 2009 in the SEER-Medicare dataset. Approximately 6% and 1% of patients with missing CCI and outlier costs, respectively, were excluded. We categorized patients by their CCI for 12 months prior to diagnosis into three categories: low (CCI = 0), medium (CCI = 1) and high (CCI = 2+). We calculated 5-years cost-effectiveness of Tx2. Patients enrolled in HMOs, lost part A and/or B, and died of causes other than colon cancer are censored. Costs are inflation adjusted to January 2009 dollars using U.S. Medical Price Index (MPI). We adjusted for censoring using Inverse Probability Weighting (IPW) method and selection bias on observables using Propensity Score Bin Bootstrapping method. Results: Among patients who received Tx1, 56% (n = 1,285) proceeded to receive Tx2. Of those who received Tx2, 67% (n = 864), 23% (n = 289), and 10% (n = 132) have low, medium and high comorbidities, respectively. Compared to those who do not received Tx2, patients who received Tx2 with low, medium, and high baseline comorbidities live 18 (se = 4), 253 (se = 4), and 183 (se = 3) days longer and incur added costs of $66,693 (se = $675), $80,217 (se = $723), and $49,610 (se = $1,136), respectively. The median Incremental Cost-Effectiveness Ratios (ICERs) of Tx2 for patients with low, medium, and high comorbidity are $80,049, $114,693, and $151,627, respectively. Conclusions: Survival benefits from receiving Tx2 vary from an average of 18 days to 253 days and added costs from $49,610 to $80,217 depending on baseline comorbidity levels. The median ICERs associated with Tx2 increase as baseline comorbidity level of patients increase.

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