P-0246 Cost-Effectiveness of Cetuximab Versus Panitumumab in Third-Line Therapy for Chemotherapy-Refractory Metastatic Colorectal Cancer in Brazil

Abstract Background Clinical management of skin-toxicity associated with the use of anti-Epidermal Growth Factor Receptor (EGFR) antibodies to treat colorectal cancer maintains quality of life of patients with colorectal cancer. Results of clinical trials have recommended the efficacy of prophylactic treatment, but the cost-effectiveness is unclear. This study examined the cost-effectiveness of preventive skin care for skin-toxicity caused by panitumumab in third-line therapy for KRAS wild type metastatic colorectal cancer from the perspective of the Japanese healthcare payer. Methods The data source was J-STEPP trial, which compared preemptive skin treatment with reactive treatment in third-line panitumumab therapy for KRAS wild type metastatic colorectal cancer in Japan. The costs and effectiveness of preemptive treatment was compared with reactive treatment in a 3-year time horizon using a 4-state partitioned survival analysis. The health outcome was quality-adjusted life-years (QALYs). The costs were 2020 revisions to the drug prices. The robustness of the model was verified by one-way sensitivity analysis and a probabilistic sensitivity analysis (PSA). A 2% annual discount was applied to the expenses and QALYs. Willingness-to-pay (WTP) threshold of 5 million JPY was used. Results Preemptive treatment had incremental effects of 0.0029 QALYs, incremental costs of 5300 JPY (48.6 USD), and incremental cost-effectiveness ratios (ICER) of 1,843,395 JPY (16,912 USD) per QALY. The variability of preemptive and reactive treatment costs for skin-toxicity and the disutility of skin-toxicity had a large impact on ICER. From PSA, the cost-effectiveness rate of preemptive treatment was 75.0%. Conclusions The cost to effectiveness of preemptive treatment to prevent skin-toxicity caused by panitumumab in third-line therapy for KRAS wild type mCRC is not high.

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Efficacy and safety of regorafenib as beyond second-line therapy in patients with metastatic colorectal cancer: an adjusted indirect meta-analysis and systematic review

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920940932 ◽

2020 ◽

Vol 12 ◽

pp. 175883592094093

Author(s):

Yinying Wu ◽

Yangwei Fan ◽

Danfeng Dong ◽

Xuyuan Dong ◽

Yuan Hu ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Meta Analysis ◽

Objective Response ◽

Cochrane Library ◽

Second Line ◽

Efficacy And Safety ◽

Line Therapy ◽

Third Line Therapy ◽

Third Line

Background: The evidence base for optimum third-line therapy for metastatic colorectal cancer (mCRC) is not conclusive. Recent studies have demonstrated the efficacy of regorafenib as third-line therapy in mCRC. This indirect meta-analysis compared the efficacy and safety of regorafenib with other available third-line therapies for mCRC. Methods: A literature search for randomized controlled trials (RCTs) was conducted in PubMed, Embase, and Cochrane Library for studies evaluating the efficacy and safety of fruquintinib, regorafenib, TAS-102, and nintedanib as third-line therapies in patients with mCRC. Overall survival (OS) and progression-free survival (PFS) were the primary outcomes, while objective response rate (ORR) and safety were the secondary outcomes. Hazard ratio (HR) and relative risk (RR) with their respective 95% confidence interval (CI) were used for analysis of survival, clinical response, and safety data. An adjusted indirect meta-analysis with placebo as the common comparator was performed. Results: We identified eight RCTs comparing regorafenib (two studies), fruquintinib (two studies), TAS-102 (three studies), and nintedanib (one study) against placebo. The OS with regorafenib was significantly better when compared with nintedanib (HR = 0.66; 95% CI: 0.45, 0.95, p = 0.02) but was similar to that of fruquintinib (HR = 1.01; 95% CI: 0.67, 1.52, p = 0.94) and TAS-102 (HR = 0.97; 95% CI: 0.68, 1.38, p = 0.88). The PFS and ORR for regorafenib were slightly better than those of TAS-102 (PFS: HR = 0.86, 95% CI: 0.54, 1.37, p = 0.5; ORR: RR = 1.13, 95% CI: 0.11, 11.05, p = 0.92) and nintedanib (PFS: HR = 0.68, 95% CI: 0.42, 1.10, p = 0.12; ORR: not reported) but were lower than those for fruquintinib (PFS: HR = 1.53, 95% CI: 0.93, 2.52, p = 0.08; ORR: RR = 0.68269, 95% CI: 0.045, 10.32, p = 0.79). Safety analysis showed that the RR of adverse events (AEs) was lesser in patients treated with regorafenib in comparison with that in patients treated with fruquintinib, but was similar to that in patients treated with nintedanib and TAS-102. Conclusion: Regorafenib has efficacy similar to that of TAS-102 and better safety when compared with fruquintinib. Considering the mechanism of action of regorafenib, which targets multiple factors in the angiogenic pathway, it could be an ideal option for treatment in the beyond second-line setting.

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Safety and tolerability profile of raltitrexed in Chinese patients with locally advanced or recurrent and metastatic colorectal cancer: A phase IV trial.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.571 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 571-571

Author(s):

Shukui Qin ◽

Jin Li ◽

Yunpeng Liu ◽

Yin Chen ◽

Nong Xu ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Locally Advanced ◽

Chinese Patients ◽

Tolerability Profile ◽

Second Line ◽

Line Therapy ◽

Third Line Therapy ◽

Third Line ◽

Phase Iv

571 Background: The clinical benefit and safety profile associated with raltitrexed in patients with advanced colorectal cancer (CRC) were established. However, safety information of raltitrexed in Chinese patients is rare. We aimed to assess the safety of raltitrexed monotherapy in Chinese patients with advanced CRC. Methods: This single-arm, open-label, multi-center, phase IV trial was conducted in 13 hospitals across China between March 2011 and July 2014. Patients with locally advanced or recurrent and metastatic colorectal cancer (mCRC) received raltitrexed (3mg/m2) as a 15-min infusion on day 1, every 21 days. Treatment was continued until disease progression or unacceptable toxicity. The primary objective was safety and the secondary objectives were disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Results: A total of 215 patients were enrolled, and the safety was assessed in 205 patients. 92 patients had 394 Adverse events (AEs) during the study. A majority (94.4%) of AEs was grade 1/2 and only 5.3% was grade 3/4. Most AEs were either resolved spontaneously or treated successfully with standard medical interventions. Severe AEs were reported by 5.8% (12/205) of patients. The most commonly reported AEs were increase of transaminases, leukopenia, nausea and vomiting. Serum transaminase elevation, an important safety concern associated with raltitrexed therapy, were transient, self-limiting and manageable. No deaths were reported during the study. The DCR in second-line and third-line therapy by raltitrexed reached 49.5% and 37.4%, respectively. The median PFS in second-line and third-line therapy was 1.43 months and 1.47 months, respectively. The median OS was 13.6 months and 8.9 months, respectively. Conclusions: Raltitrexed monotherapy is a safe, well-tolerated and convenient therapy option for Chinese patients. The treatment-associated toxicity is manageable and does not lead to discontinuation of treatment in oncology practice.

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276 Promising activity with capecitabine and mitomycin C (MMC) as third line therapy for patients with metastatic colorectal cancer (MCRC) resistant to fluorouracil (5-FU) and irinotecan: results of a phase II study

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(03)90309-0 ◽

2003 ◽

Vol 1 (5) ◽

pp. S85

Author(s):

J.L.B. Dickson ◽

S. Rao ◽

M.E. Hill ◽

T.J. Price ◽

A.R. Norman ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Mitomycin C ◽

Phase Ii ◽

Phase Ii Study ◽

Line Therapy ◽

Third Line Therapy ◽

Third Line

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Efficacy and safety of regorafenib as third-line therapy in metastatic colorectal cancer: An indirect meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.119 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 119-119

Author(s):

Yinying WU ◽

Yangwei Fan ◽

Dan Feng Dong ◽

Xuyuan Dong ◽

Yuan Hu ◽

...

Keyword(s):

Colorectal Cancer ◽

Relative Risk ◽

Metastatic Colorectal Cancer ◽

Meta Analysis ◽

Cochrane Library ◽

Secondary Outcome ◽

Efficacy And Safety ◽

Line Therapy ◽

Third Line Therapy ◽

Third Line

119 Background: The evidence base for optimum third-line therapy for metastatic colorectal cancer (mCRC) is not conclusive. Recent studies have demonstrated the efficacy of regorafenib as third-line therapy in mCRC. This indirect meta-analysis compared the efficacy and safety of regorafenib in comparison to other available third-line therapies in mCRC. Methods: Literature search for randomized controlled trials was conducted in PubMed, Embase and Cochrane library for studies evaluating the efficacy and safety of fruquintinib, regorafenib, TAS-102 and nintedanib as third-line therapies in mCRC patients. The primary outcomes included overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) and safety as the secondary outcome. Hazard ratio (HR) and relative risk (RR) with their respective 95% confidence interval (CI) were used for analysis of survival, clinical response and safety data, respectively. An adjusted indirect meta-analysis with placebo as the common comparator was performed. Results: We identified 8 RCTs studies comparing regorafenib (2 studies), fruquintinib (2 studies), TAS-102 (3 studies) and nintedanib (1 study) against placebo. The OS with regorafenib was significantly better when compared to nintedanib (HR= 0.66, 95% CI 0.45, 0.95, p=0.02), but was similar to that of fruquintinib (HR=1.01, 95% CI 0.67, 1.52, p=0.94) and TAS-102 (HR= 0.97, 95% CI 0.68, 1.38, p=0.88). The PFS and ORR for regorafenib were slightly better than TAS-102 (PFS: HR= 0.86, 95% CI 0.54, 1.37, p=0.5; ORR: RR= 1.13, 95% CI 0.11, 11.05, p=0.92) and nintedanib (PFS: HR= 0.68, 95% CI 0.42, 1.10, p=0.12, ORR: not reported) but was lower than fruquintinib (PFS: HR= 1.53, 95% CI 0.93, 2.52, p=0.08; ORR: RR= 0.68269, 95% CI 0.045, 10.32, p=0.79). Safety analysis showed that the relative risk of adverse events was lesser in patients treated with regorafenib in comparison to fruquintinib but was similar to that of nintedanib and TAS-102. Conclusions: Regorafenib with its efficacy and safety coupled with comprehensive continuously anti-angiogenic therapy, might be the first option in third-line mCRC. Head-on comparisons are required for further validation.

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