By Hisanaga Nomura, Deputy Manager, Japan Agency for Medical Research and Development, Japan
Every year, the European Society for Medical Oncology (ESMO) Congress is held in autumn.
This year, it was held virtually due to the ongoing coronavirus pandemic. The registration was free, and I was able to participate in the ESMO Congress held in Japan without paying high travel expenses and taking time off from work. I found an interesting presentation at the ESMO Congress to introduce you to. Furthermore, I would like to introduce our approach in Japan in this regard.
Oxaliplatin is a key chemotherapeutic agent used in the treatment of colorectal cancer. During a special session at the ESMO 2017 Congress held in Vienna, the efficacy of 3- and 6-month oxaliplatin-based adjuvant chemotherapy for colon cancer was reported. The results of the IDEA collaboration (N = 10,500), which combined several studies, did not reach statistical significance, but a 3-month treatment was recommended in individuals with stage III disease, except for high-risk patients1. During the 2020 ASCO Annual Meeting, the final result of the IDEA collaboration were presented, and the overall survival and 5-year disease-free survival rates in colon cancer patients who received chemotherapy suggested that further discussion on this matter is no longer needed. Results of the sub-analysis of TOSCA study2, one of the IDEA collaborations, were reported during the ESMO 2020 Virtual Congress (Lonardi et al. ESMO 2020, #3390). Data on the safety and efficacy of chemotherapy in older patients are difficult to interpret as these patients are underrepresented in clinical trials. Data from two prospective clinical trials3,4 and retrospective real-world analysis5 confirmed that the survival benefit of 5-FU/LV treatment in patients aged ≥65 years with stage III disease only marginally increased when it was combined with oxaliplatin treatment. Despite evidence on the uncertain size benefit of adjuvant therapy in older patients, the use of adjuvant chemotherapy in this patient population has reduced in clinical practice.
The impact of patient age (<70 years vs. ≥70 years) on the efficacy of oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer enrolled in the TOSCA trial was evaluated, regardless of the randomization arm. Of the 2,360 patients with stage III disease enrolled in the TOSCA trial, 1,667 patients were aged 70 years and 693 patients were aged <70 years. The treatment regimen (FOLFOX and CAPOX) and duration (3 months and 6 months) were equally distributed between the two age groups. A higher incidence of relapse was observed in the older age group than in the younger age group (24.2% vs. 20.3%, p = 0.033). However, multivariate analysis of the relapse-free interval showed that age did not have a significant effect on the efficacy of oxaliplatin-based adjuvant chemotherapy (hazard ratio: 1.19, 95% confidence interval: 0.98-1.44, p = 0.082). This finding showed that different prognostic factors and possibly reduced compliance may account for the observed small reduction in the benefit of chemotherapy in older adults. Patients aged <70 years showed lower compliance and inferior relapse-free survival than those aged <70 years. The significance of oxaliplatin treatment cannot be derived from this analysis and will not change daily practice at this time.
Similar to the presentation in the ESMO 2020 Virtual Congress, the method of implementing the standard therapy for older cancer patients has been increasingly discussed. Quality of life (QOL) was set as the second endpoint in the clinical trial.
The super-aging society has become an inevitable problem not only in Japan but also worldwide. The implication of high medical costs related to colon cancer treatment in the national budget is a concern.
The National Institute for Health and Care Excellence developed the EQ5D analysis technique. EQ5D is considered as a method that can be used to assess the health-related QOL in individuals with various diseases for health economic assessment techniques.
The field of pharmaco-economics is not sufficiently developed in Japan. Hence, there is a need for evaluating the knowledge of Japanese pharmacists regarding this field.
Shimizu et al. devised a development plan for collecting the data on the daily routine of pharmacists using the EQ5D instrument.
First, the utility value was measured to make accurate generalizations regarding community pharmacists.
In collaboration with community pharmacists, data on the side effects of chemotherapy drugs based on patient-reported outcomes were obtained through a face-to-face pharmaceutical interview.
As next steps, hospital pharmacists should measure the utility value of each regimen. Furthermore, the differences in health-related QOL in older patients should be assessed to compare the changes in treatment duration of FOLFOX and CAPOX.
I hope that this study, in collaboration with hospital pharmacists and community pharmacists, will yield good results and that cost-effectiveness research involving older patients with cancer will become part of the pharmacist's role.
<References>
1. Grothey A, Sobrero AF, Shields AF, et al: Duration of Adjuvant Chemotherapy for Stage III Colon Cancer. N Engl J Med 378:1177-1188, 2018
2. Sobrero A, Lonardi S, Rosati G, et al: FOLFOX or CAPOX in Stage II to III Colon Cancer: Efficacy Results of the Italian Three or Six Colon Adjuvant Trial. J Clin Oncol 36:1478-1485, 2018
3. Yothers G, O'Connell MJ, Allegra CJ, et al: Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol 29:3768-74, 2011
4. Tournigand C, Andre T, Bonnetain F, et al: Adjuvant therapy with fluorouracil and oxaliplatin in stage II and elderly patients (between ages 70 and 75 years) with colon cancer: subgroup analyses of the Multicenter International Study of Oxaliplatin, Fluorouracil, and Leucovorin in the Adjuvant Treatment of Colon Cancer trial. J Clin Oncol 30:3353-60, 2012
5. Hanna NN, Onukwugha E, Choti MA, et al: Comparative analysis of various prognostic nodal factors, adjuvant chemotherapy and survival among stage III colon cancer patients over 65 years: an analysis using surveillance, epidemiology and end results (SEER)-Medicare data. Colorectal Dis 14:48-55, 2012
