Adjuvant Chemotherapy In Elderly Patients Research Articles

HPB SO41 - Does Adjuvant Chemotherapy Provide a Survival Benefit in Elderly Patients (≥70 years) with Pancreatic Cancer? A Retrospective Cohort-study

Abstract Background There is currently conflicting evidence surrounding the use of adjuvant chemotherapy (AC) for elderly patients (over 70 years) with pancreatic adenocarcinoma. Limited existing studies debate its effect on overall survival (OS) and relapse-free survival (RFS). The aim of this study is to assess whether adjuvant chemotherapy following pancreaticoduodenectomy provides a survival benefit in elderly patients with pancreatic cancer. Method A retrospective review including elderly adult patients, seventy years and older, who underwent a Whipple’s pancreatoduodenectomy for pancreatic adenocarcinoma between 1st January 2015 and 31st December 2020, at a tertiary HPB centre was performed. Information on baseline characteristics, preoperative assessment, histopathology, postoperative complications and course, and adjuvant chemotherapy were collected. Elderly patients who received AC were compared to those who did not undergo AC. Statistical analysis was performed using Jamovi 2.3. Results Sixty-eight patients were included with 44 (65%) receiving AC. There was no difference in age (p=0.72), sex (p=0.19), preoperative characteristics (all p<0.05), and resection margin (p=0.67) between the groups. There was no difference in complication rates (p=0.20), including Clavien-Dindo3+ (p=0.68). The length of hospital stay was shorter in the AC group, without statistical significance (15.7±11.9 vs 23.2±20.3 days, p=0.06). There was no difference in RFS between the groups (22.7±20 vs 15.4±23.6 months, p=0.18). However, patients who received AC had a significantly greater OS compared to those who did not (30.7±18.2 vs 18.6±22.2 months, p=0.02). Conclusion AC improved overall survival in elderly (≥70 years) patients with pancreatic adenocarcinoma. Whilst many elderly patients may not receive adjuvant chemotherapy due to postoperative complications and/or longer hospital stay, our study suggests age alone should not be a deciding factor when considering adjuvant chemotherapy in this cohort. A future large, multicentre prospective study is needed to further examine OS with the use of AC in elderly patients with pancreatic adenocarcinoma.

1224P Evaluation of safety and feasibility of adjuvant chemotherapy in elderly patients with primary non-small cell lung cancer

1224P Evaluation of safety and feasibility of adjuvant chemotherapy in elderly patients with primary non-small cell lung cancer

Benefits of adjuvant chemotherapy in elderly patients with stage IB-IIIB non-small cell lung cancer: a propensity-matched analysis.

Adjuvant chemotherapy (ACT) is a well-recognized and well-established treatment for surgically resected non-small cell lung cancer (NSCLC), but its suitability for elderly patients remains controversial. Further investigation is warranted to guide ACT decisions in this demographic. We extracted data from the Surveillance, Epidemiology, and End Results (SEER) database, focusing on patients aged 70 years or older who underwent surgical resection for stage IB, II, or III NSCLC as per the 7th edition of the American Joint Committee on Cancer staging system (AJCC 7th edition). Propensity score matching (PSM), Kaplan-Meier analysis, and Cox regression were employed for statistical analyses. There were 503 participants received ACT in this study of 2,000 patients aged 70 or older with stage IB-IIIB NSCLC who underwent surgical resection without preoperative chemotherapy. Overall, ACT did not significantly correlate with extended overall survival (OS) (P=0.07) compared to non-ACT. After 2:1 PSM, the matched cohort comprised 317 non-ACT and 206 ACT recipients. Post-PSM, the ACT group exhibited improved OS (P=0.044) compared to the non-ACT group. Cox regression analysis identified gender, primary tumor site, histologic grade, N stage, and ACT as independent predictors of OS (P<0.05). Subgroup analysis indicated amplified ACT benefits in individuals aged 70-79 years, male, with N1 stage, or those without radiotherapy. ACT may confer benefits to elderly stage IB-IIIB NSCLC patients, particularly those aged 70-79 years, male, and with N1 stage.

Adjuvant chemotherapy for elderly patients with colorectal cancer: a single-centre observational study in Japan

Adjuvant chemotherapy improves the prognosis of patients with colorectal cancer (CRC) following radical resection. The aim of the present study is to review appropriate chemotherapeutic regimens for elderly patients. We examined 1138 Japanese patients who were operated for high-risk stage II or stage III CRC between July 2010 and June 2021 at our hospital. Patients were divided according to an age of 70 years. The efficacy of adjuvant therapy was analyzed in association with age and adjuvant chemotherapeutic regimens. A total of 507 patients (45%) were ≥70 years old. They were less likely to receive adjuvant chemotherapy (p < 0.001) or palliative chemotherapy after recurrence (p < 0.001) than patients aged <70 years. Cancer-specific survival (CSS) in stage III CRC patients was longer in the <70 years group than in the ≥70 years group (p = 0.006); however, CSS by regimens did not significantly differ between these groups. Adjuvant chemotherapy was associated with the longer relapse-free survival of stage III CRC patients in the <70 years group (p = 0.005). Although adjuvant chemotherapy was associated with a favourable CSS regardless of age, the implementation rate of adjuvant chemotherapy for elderly CRC patients was low, which may explain shorter CSS in stage III CRC patients the ≥70 years group than in the <70 years group.

Benefit of Adjuvant Chemotherapy for Patients Older Than 75 Years With Completely Resected p-Stage II-IIIA Non–Small-Cell Lung Cancer: A Retrospective Cohort Study Using Japanese Nationwide Real-World Data

BackgroundThe efficacy of adjuvant chemotherapy (ACT) in elderly patients with completely resected p-stage II-IIIA non–small-cell lung cancer (NSCLC) remains unclear because all previous randomized controlled trials on ACT have been conducted among patients aged <75 years. Thus, this study aimed to evaluate the effectiveness of ACT in elderly patients with completely resected NSCLC. PatientsWe extracted the nationwide data of 812 patients aged ≥75 years who underwent lobectomy with mediastinal nodal dissection in 2010 and were diagnosed with p-stage II-IIIA NSCLC, from nationwide registry data accumulated in 2016. MethodsWe classified the 812 patients into 2 groups based on the ACT administration status and analyzed the differences in their postoperative overall survival (OS). ResultsOverall, 295 patients received ACT (36.3%; group A), whereas 517 patients did not (63.70%; group N). Group A showed significantly better OS as a whole (hazard ratio [HR]: 0.650 [95% confidence interval {CI}: 0.526-0.804]), in the p-stage II subset (HR: 0.688 [95% CI: 0.513-0.925]), and p-stage IIIA subset (HR: 0.547 [95% CI: 0.402-0.743]) than group N. Even after propensity score matching, group A showed significantly better OS as a whole (HR: 0.626 [95% CI: 0.495-0.792]), in the p-stage II subset (HR: 0.690 [95% CI: 0.493-0.964]), and p-stage IIIA subset (HR: 0.554 [95% CI: 0.398-0.772]) than group N. ConclusionACT is recommended even in elderly patients with completely resected p-stage II-IIIA NSCLC. Hence, physicians should not avoid ACT in patients with completely resected NSCLC based solely on age.

Estimating Treatment Effect of Adjuvant Chemotherapy in Elderly Patients With Stage III Colon Cancer Using Bayesian Networks.

While adjuvant therapy with capecitabine and oxaliplatin (CAPOX) has been proven to be effective in stage III colon cancer, capecitabine monotherapy (CapMono) might be equally effective in elderly patients. Unfortunately, the elderly are under-represented in clinical trials and patients included may not be representative of the routine care population. Observational data might alleviate this problem but is sensitive to biases such as confounding by indication. Here, we build causal models using Bayesian Networks (BNs), identify confounders, and estimate the effect of adjuvant chemotherapy using survival analyses. Patients 70 years and older were selected from the Netherlands Cancer Registry (N = 982). We developed several BNs using constraint-based, score-based, and hybrid algorithms while precluding noncausal relations. In addition, we created models using a limited set of recurrence and survival nodes. Potential confounders were identified through the resulting graphs. Several Cox models were fitted correcting for confounders and for propensity scores. When comparing adjuvant treatment with surgery only, pathological lymph node classification, physical status, and age were identified as potential confounders. Adjuvant treatment was significantly associated with survival in all Cox models, with hazard ratios between 0.39 and 0.45; CIs overlapped. BNs investigating CAPOX versus CapMono did not find any association between the treatment choice and survival and thus no confounders. Analyses using Cox models did not identify significant association either. We were able to successfully leverage BN structure learning algorithms in conjunction with clinical knowledge to create causal models. While confounders differed depending on the algorithm and included nodes, results were not contradictory. We found a strong effect of adjuvant therapy on survival in our cohort. Additional oxaliplatin did not have a marked effect and should be avoided in elderly patients.

Is adjuvant chemotherapy for completely resected p-stage IA (>2cm) and stage IB non-small-cell lung cancer beneficial for elderly patients? A large, retrospective cohort study based on real-world data from Japan.

The efficacy of tegafur-uracil as adjuvant chemotherapy for patients with completely resected stage I non-small-cell lung cancer is proven; however, its efficacy for elderly patients remains unclear. Herein, we evaluated the effectiveness of adjuvant chemotherapy for elderly patients with completely resected stage I non-small-cell lung cancer based on real-world Japanese data using propensity score matching. This retrospective study extracted data from a nationwide registry study, performed in 2016, on patients ≥75years who underwent lobectomy with mediastinal nodal dissection for non-small-cell lung cancer in 2010 and were diagnosed with p-stage IA (>2cm) or stage IB non-small-cell lung cancer. We classified the 1294 patients into two groups-Group A, postoperative adjuvant chemotherapy (n=295, 22.8%) and Group N, no adjuvant chemotherapy (n=999, 77.2%)-and analyzed differences in postoperative overall survival between groups. Group A showed no advantage in overall survival over Group N as a whole (hazard ratio: 0.824 [95% confidence interval: 0.631-1.076]), in p-stage IA (hazard ratio: 0.617 [95% confidence interval: 0.330-1.156]) and in p-stage IB (hazard ratio: 0.806 [95% confidence interval: 0.597-1.088]) subsets. Even after propensity score matching, Group A showed no significant advantage in overall survival over Group N as a whole (hazard ratio: 0.975 [95% confidence interval: 0.688-1.381]), in p-stage IA (hazard ratio: 1.390 [95% confidence interval: 0.539-3.586]) and in p-stage IB (hazard ratio: 0.922 [95% confidence interval: 0.633-1.343]). adjuvant chemotherapy for completely resected p-stage IA (>2cm) and stage IB non-small-cell lung cancer showed no benefit for recommendation for elderly patients; considering the risk of adverse events, we do not recommend adjuvant chemotherapy for elderly patients.

Prognostic model for predicting the survival benefit of adjuvant chemotherapy for elderly patients with stage II colon cancer: a population-based study.

Adjuvant chemotherapy benefits in elderly patients with stage II colon cancer (CC) remain controversial. We aimed to construct a nomogram to estimate the chemotherapy survival benefits in elderly patients. The training and testing cohort were patients with stage II CC older than 70 years from the Surveillance, Epidemiology, and End Results (SEER) database, while the external validation cohort included patients from the National Cancer Center (NCC). Cox proportional hazard models were used to determine the covariates associated with overall survival (OS). Using the risk factors identified by Cox proportional hazards regression, a nomogram was developed to predict OS. Nomogram precision was assessed using receiver operating characteristic and calibration curves. The present study recruited 42 097 and 504 patients from the SEER database and NCC, respectively. The OS of patients who underwent surgery plus adjuvant chemotherapy was considerably longer than patients who underwent surgery alone. The nomogram included variables related to OS, including age, year of diagnosis, sex, AJCC T stage, tumor location, tumor size, harvested lymph nodes, and chemotherapy. According to the nomogram score, the elderly patients were separated into high- and low-risk groups, with high-risk group nomogram scores being greater than the median value, and vice versa. Patients in the high-risk group witnessed worse prognosis and were more likely to benefit from postoperative chemotherapy. This nomogram can be regarded as a useful clinical tool for assessing the potential adjuvant chemotherapy benefits and for predicting survival in elderly patients with stage II CC.

Adjuvant Chemotherapy in Older Patients with Gastric Cancer: A Population-Based Cohort Study.

(1) Background: The effectiveness of adjuvant chemotherapy in older patients with gastric cancer after D2-gastrectomy is unclear. This study investigated the efficacy of adjuvant chemotherapy in elderly patients with stage II/III gastric cancer. (2) Methods: A real-world population-based retrospective cohort of patients aged ≥65 with stage II/III gastric cancer (n = 2616; median age: 73.5; 12.2% aged >80 years) treated between 1 January 1997 and 31 December 2020 were included. All data was retrieved from the Hong Kong Hospital Authority Clinical Management System (CMS). Clinical characteristics of those patients with and without adjuvant chemotherapy treatment were balanced after propensity score matching (PSM). In total, 732 patients treated with adjuvant chemotherapy were matched with 732 patients treated with surgery alone. Hazard ratios (HRs) estimated via Cox proportional hazards regression models were used to compare the overall survival (OS) and cancer-specific survival (CSS) of the two patient groups. (3) Results: Adjuvant chemotherapy was associated with better OS (37 vs. 25 months; HR: 0.80; 95% CI: 0.75-0.84; p < 0.001) than surgery alone. The OS benefit was observed in both the 65-80 (44 vs. 27 months; HR: 0.79; 95% CI: 0.74-0.84; p < 0.001) and >80 (14 vs. 11 months; HR: 0.82; 95% CI: 0.71-0.96; p < 0.001) age groups. A better CSS was observed in patients who received adjuvant chemotherapy than those who only had surgery (5-year CSS: 64.1% vs. 61.1%, HR: 0.85; 95% CI: 0.79-0.93; p < 0.001). (4) Conclusions: adjuvant chemotherapy significantly improved OS and CSS in older patients with stage II/III gastric cancer.

Survival benefit of adjuvant chemotherapy in elderly patients with stage I triple-negative breast cancer: a cohort study based on the SEER database.

This study analyzed the trend and prognostic role of postoperative adjuvant chemotherapy (POCT) in patients with stage I triple-negative breast cancer (TNBC) aged more than 65 years. In addition, the relationship between POCT and survival rate was also determined. The Surveillance, Epidemiology, and End Results (SEER) database was collected to determine 3,307 TNBC elderly women aged ≥65 years between 2010 and 2016, and they were divided into POCT and non-POCT groups. Propensity score matching (PSM) method was used to offset the differences in baseline characteristics between the groups. Kaplan-Meier plots were tested to contrast overall survival (OS) and breast cancer-specific survival (BCSS) between the two groups. The Cox proportional hazard model was constructed to assess the prognostic factors affecting OS and BCSS. Younger age, higher histological grade, married, postoperative radiotherapy, lumpectomy, larger tumor, and closer year of diagnosis were related to an enhanced likelihood of adjuvant chemotherapy. After PSM, POCT was related to increased 5-year OS [hazard ratio (HR): 0.571, 95% confidence interval (CI): 0.432-0.753, respectively], without significant difference in BCSS improvement. Exploratory subgroup analysis demonstrated that POCT contributed to OS improvement in both IA and IB patients, but did not improve BCSS in IA and IB patients. In elderly patients ≥65 years, POCT improved 5-year OS in stage I TNBC patients, while further exploration with larger prospective trials are needed.

Role of adjuvant chemotherapy (CT) in node negative 4-5 cm non-small cell lung cancer in elderly population.

e20615 Background: The role of adjuvant CT for 4-5 cm primary lung tumors without any regional lymph node involvement following surgical resection is somewhat controversial. While it is favored in most cases, it should be individualized depending on other pathological risk factors and the patient's performance status. In this study, we investigated the benefit of adjuvant CT in elderly patients with 4-5 cm tumor size following complete surgical resection. Methods: We utilized Surveillance, Epidemiology, and End Results Program (SEER) database to identify elderly patients (≥65 years) with 4 to 5 cm sized non-small cell lung cancer after complete surgical resection diagnosed from 2010-2015. The baseline characteristics among the patients who received and didn’t receive adjuvant CT were compared using relevant parametric/non-parametric tests. Kaplan Meir curve was generated for the univariate survival analysis, and the log-rank test was used for comparison. Multivariate survival analysis was done using the cox proportional hazards regression model. Results: The database included 2582 patients. Among them, 492 (19.1%) cases had received adjuvant chemotherapy while 2090 (80.9%) cases had not. The population that received chemotherapy was younger than those that did not (Median:75 years vs 71 years, p &lt; 0.001). The 5-year overall survival for patients who received chemotherapy was significantly higher than those who did not (53.9% vs 46.5%, P = 0.002). On the multivariate analysis adjusted for age, gender, race, income status, and type of surgery, cases with adjuvant chemotherapy had lower hazards as compared to those who had not received adjuvant chemo (Hazard Ratio (HR):0.86, confidence interval (CI): [0.75,0.99], P value = 0.04). Conclusions: Our study demonstrated a survival benefit with adjuvant CT for node-negative NSCLC of 4-5 cm size in the elderly population.

P-269 Efficacy and safety of doublet adjuvant chemotherapy for elderly patients with stage III colorectal cancer

P-269 Efficacy and safety of doublet adjuvant chemotherapy for elderly patients with stage III colorectal cancer

Randomized phase II study of daily versus alternate-day administrations of S-1 for the elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm)-IIIA of non-small cell lung cancer: Setouchi Lung Cancer Group Study 1201.

It is shown that the postoperative adjuvant chemotherapy for non-small cell lung cancer (NSCLC) was associated with survival benefit in an elderly population. We aimed to analyze the feasibility and efficacy of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm) to IIIA (UICC TNM Classification of Malignant Tumours, 7th edition) NSCLC. Elderly patients were randomly assigned to receive adjuvant chemotherapy for one year consisting of either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Arm A) or a daily oral administration of S-1 (80 mg/m2/day) for 14 consecutive days followed by 7-day rest (Arm B). The primary endpoint was feasibility (treatment completion rate), which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more. We enrolled 101 patients in which 97 patients received S-1 treatment. The treatment completion rate at 6 months was 69.4% in Arm A and 64.6% in Arm B (p = 0.67). Treatment completion rate in Arm B tended to be lower compared to Arm A, as the treatment period becomes longer (at 9 and 12 months). RDI of S-1 at 12 months and completion of S-1 administration without dose reduction or postponement at 12 months was significantly better in Arm A than in Arm B (p = 0.026 and p < 0.001, respectively). Among adverse events, anorexia, skin symptoms and lacrimation of any grade were significantly more frequent in Arm B compared with Arm A (p = 0.0036, 0.023 and 0.031, respectively). The 5-year recurrence-free survival rates were 56.9% and 65.7% for Arm A and B, respectively (p = 0.22). The 5-year overall survival rates were 68.6% and 82.0% for Arm A and B, respectively (p = 0.11). Although several adverse effects were less frequent in Arm A, both alternate-day and daily oral administrations of S-1 were demonstrated to be feasible in elderly patients with completely resected NSCLC. Unique ID issued by UMIN: UMIN000007819 (Date of registration: Apr 25, 2012) https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009128. Trial ID issued by jRCT: jRCTs061180089 (Date of registration: Mar 22, 2019, for a shift toward a "specified clinical trial" based on Clinical Trials Act in Japan) https://jrct.niph.go.jp/en-latest-detail/jRCTs061180089.

Relevance of adjuvant chemotherapy in elderly patients with low rectal tumors.

37 Background: The balance between the benefits and toxicities of adjuvant systemic chemotherapy is crucial in the elderly, and often co-morbid patients who have undergone total mesorectal excision (TME) surgery for carcinomas of the lower rectum (1). Tumour distance from the anal verge is a known prognostic factor in rectal cancer (2, 3) and it may influence the effectiveness of adjuvant chemotherapy (AC) (4). This study evaluated the differences in the survival outcomes between patients on surveillance(S) and those who received AC in a multi-centre, real-world setting with a focus on the elderly cohort. Methods: Data was extracted from electronic patient records from 4 NHS trusts in Kent, UK. We retrospectively analysed records of patients between 1 Jan 2014 and 31 Dec 2019, who had neoadjuvant chemoradiotherapy, were down-staged and then offered either S or AC based on clinician’s judgement. The tumour distance from the anal verge was measured through high resolution MRI. The patients were downstaged following assessment as their pTNM staging was lower than their cTNM staging. Results: 589 patients treated for rectal cancer were identified. Of these, 168/589(28%) had non-metastatic disease, were later down-staged at TME and were offered S or AC. 95/168 (57%) of these patients received AC. Patients who received AC were younger (median age 63 vs 70 years, p&lt; 0.001) and with additional poor prognostic factors such as extramural venous invasion EMVI+ (74 vs 39%, p= 0.001), circumferential resection margin CRM+ (89 vs 70% p = 0.001) and pathological nodal involvement (AJCC stage III disease) ( p&lt; 0.001) (table) compared to those on S. Our findings did suggest that patients on surveillance with tumours &lt; 5cm from the anal verge had a longer disease-free survival(DFS) than those who received chemotherapy; this was especially the case in the elderly patient cohort (HR 0.13 95% CI 0.02-0.99, p= 0.049).Our findings also showed that the DFS benefit for patients under surveillance increased with age. Surveillance was most effective in patients over 60 years old compared to those under 60. However, age or distance from anal verge did not have an impact on overall survival (HR 1.01 95% Cl 0.95-1.08 p= 0.70). Conclusions: Although patients treated with AC were younger than patients on S, their tumours had additional poor prognostic factors. Patients on surveillance with tumours &lt;5cm from the anal verge enjoyed a longer DFS but no OS benefit. Elderly patients with tumours &lt; 5cm from the anal verge with no poor prognostic features could derive a benefit from surveillance and avoid chemotherapy-related toxicity. However, our findings will need to be corroborated in prospective studies. [Table: see text]

ASCO 2022 Breast Cancer Updates

"Data presented at ASCO 2022 provide new perspectives of therapy for patients with breast cancer. Starting with the plenary session with DESTINY-Breast04 we are turning a new page in the treatment of metastatic human epidermal growth factor receptor 2 (HER2)-low breast cancer patients. The results of the DESTINY-Breast04 trial open a new therapeutic option for half of the patients with metastatic breast cancer, establishing HER2-low metastatic breast cancer as a targetable population with trastuzumab deruxtecan. The indications for antibody drug conjugates are expanding to patients with metastatic hormone receptor positive endocrine resistant disease based on TROPICS-02. From the multitude of clinical trials with antibody drug conjugates, we can envision that this will be likely the new way to deliver chemotherapy in the future. Differences in survival within the three cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in upfront metastatic hormone positive breast cancer are emerging. We have data on continuation of ribociclib beyond disease progression on CDK4/6 in the MAINTAIN trial. The FAKTION trial does prove the benefit of the AKT inhibitor capivasertib and does highlight the importance of an extended molecular panel of the phosphatidylinositol3-kinase PI3K pathway. Furthermore, the exploratory analysis of KEYNOTE- 522, examining the correlation of event free survival and residual cancer burden after neoadjuvant treatment in patients with triple negative breast cancer does demonstrate a benefit of pembrolizumab extending to patient which did not achieve pathologic complete response, mainly by a decrease in residual cancer burden. Advances in biomarkers of response to immunotherapy are needed. For early stage breast cancer studies are in support of de-escalation of radiotherapy for low risk breast cancer patients and confirming the lack of benefit of adjuvant chemotherapy for elderly patients, even with high genomic grade index."

Effectiveness of adjuvant chemotherapy for elderly patients with triple-negative breast cancer.

There is little evidence determining whether elderly patients (from 70 to 90 years old) with triple-negative breast cancer could benefit from adjuvant chemotherapy (AC). This study explores the effect of AC in these population following surgery. A total of 4610 patients were identified in the Surveillance, Epidemiology, and End Results database (2010-2018). Multiple imputation by chained equations was performed to impute missing data. Inverse probability of treatment weighting (IPTW) was applied to reduce the selection bias. IPTW-adjusted Kaplan-Meiers survival analysis and Cox proportional hazards models were performed to compare breast cancer specific survival (BCSS) and overall survival (OS) in the two treatment groups. The patients were classified into the chemotherapy (n=1989) and the observation (n=2621) groups. The percentage of patients receiving AC versus observation increased significantly from 2010 to 2018 (estimated annual percentage change, 1.49%; 95%CI, 0.75-2.16%, p=0.002). The 5-year IPTW-adjusted rates of BCSS and OS in AC group were better than that in observation group (BCSS: 82.32% vs. 78.42%, p=0.010; OS: 75.54% vs. 64.65%, p<0.001). The patients could benefit from AC based on the results of IPTW-adjusted Cox proportional hazards regression analysis (BCSS: HR, 0.77, 95%CI, 0.62-0.94, p=0.012; OS: HR, 0.66, 95%CI, 0.57-0.78, p<0.001). AC was associated with a significant outcome benefit across the year at diagnosis, marital status, stage, lymph node, surgery, and radiation subgroups (all p<0.050). Patients with T1ab could not benefit from AC (p>0.050). In conclusion, we presented a BCSS and OS benefit from AC in elderly patients with triple-negative breast cancer (TNBC). AC remained a reasonable treatment approach in these specific patients. For the patients with T1ab, de-escalated treatment would be administrated with caution.

Survival Outcomes of Adjuvant Chemotherapy in Elderly Patients with Stage III Colon Cancer.

BackgroundThe survival impact of multi-agent (MAC) compared with single-agent (SAC) adjuvant chemotherapy (AC) in elderly patients with stage III colon cancer (CC) remains controversial. The aim of this study was to compare survival outcomes of MAC and SAC in this population utilizing the National Cancer Database (NCDB).Patients and MethodsPatients aged ≥70 years with pathological stage III CC diagnosed in 2004-2015 were identified in the NCDB. Univariate and multivariable analyses were conducted, and Kaplan-Meier analysis and Cox proportional hazard models were used to identify associations between MAC vs. SAC and overall survival (OS).ResultsAmong 41 707 elderly patients (≥70 years old) with stage III CC, about half (n = 20 257; 48.5%) received AC; the majority (n = 12 923, 63.8%) received MAC. The median age was 79 (range 70-90). The majority were female (n = 11 201, 55.3%), Caucasians (88%) and had moderately differentiated tumor grade (n = 12 619, 62.3%), tumor size >4 cm (11 785, 58.2%), and negative surgical margins (18 496, 91.3%). Low-risk stage III CC constituted 50.6% (n = 10 264) of the study population. High-risk stage III CC was associated with worse OS compared with low-risk disease (HR 0.35, 0.34-0.36, P < .001). Multi-agent chemotherapy was associated with a better 5-year OS compared with SAC (P < .001). High-risk stage III patients who received MAC vs. SAC had an OS of 4.2 vs. 3.4 years, respectively (P < .001). Low-risk stage III patients who received MAC vs. SAC had a median OS of 8.5 vs. 7 years (P < .001). In univariate and multivariable analyses, male sex, positive surgical margin, insurance and facility types, age, year of diagnosis, tumor size, and Charlson-Deyo score of >2 were associated with worse OS (P < .05).ConclusionsAny adjuvant chemotherapy has a trend of survival benefits. Multi-agent chemotherapy seems to have an enhanced benefit in the 70-75 age group. Multi-agent chemotherapy seemed to have similar efficacy as SAC in those aged >76 years.

Management of elderly patients with bone and soft tissue sarcomas: JCOG Bone and Soft Tissue Tumor Study Group.

Approximately, 40% of bone sarcomas and 60% of soft tissue sarcoma arise in patients aged ≥65years. However, because sarcoma is very rare, there is little evidence regarding the management of elderly patients with sarcoma. Age has been reported as a prognostic factor in patients with sarcomas. The standard therapy for all localized bone and soft tissue sarcomas is surgical resection, even in elderly patients. Radiation or ion-beam therapy can be considered for unresectable sarcomas. Although adjuvant chemotherapy is standard for osteosarcoma, the usefulness of adjuvant chemotherapy for elderly patients has not been verified; therefore, it may not be recommended for elderly patients with osteosarcoma. For elderly patients with advanced osteosarcoma, if general conditions permit, doxorubicin- and/or ifosfamide-based regimens as well as molecular-targeted therapies, including sorafenib, regorafenib and everolimus, may be considered, although these drugs have not been approved for sarcoma in Japan. Adjuvant chemotherapy with doxorubicin plus ifosfamide is recommended for patients with high-risk localized soft tissue sarcoma if they are aged ≤70years. For first-line treatment of advanced soft tissue sarcoma in elderly patients, doxorubicin monotherapy is considered to be the standard regimen, and pazopanib can be an alternative. For second-line treatment, gemcitabine-based regimens, pazopanib, trabectedin and eribulin may be options for elderly patients with advanced soft tissue sarcoma.

Cost-Effectiveness of Trastuzumab With or Without Chemotherapy as Adjuvant Therapy in HER2-Positive Elderly Breast Cancer Patients: A Randomized, Open-Label Clinical Trial, the RESPECT Trial

Background and ObjectiveTrastuzumab is a standard care as adjuvant chemotherapy (AdjCT) for patients with human epidermal growth factor receptor 2 (HER2)-positive primary breast cancer (BC) in Japan. However, no reports have evaluated its economics for patients with HER2-positive BC over 70 years of age. The objective of this study was to evaluate the cost-effectiveness of HER2-targeted trastuzumab + chemotherapy in Japan, comparing it with trastuzumab monotherapy.MethodsA three-state-partitioned survival model was developed to evaluate the cost-effectiveness of trastuzumab + chemotherapy versus trastuzumab monotherapy for AdjCT in elderly patients with HER2-positive BC. We derived the efficacy data, utilities, and costs of both arms from individual patient data in the RESPECT trial (NCT01104935) and published studies. The costs and quality-adjusted life years (QALYs) were discounted at 2% per annum using a payer perspective. The respective cost estimates were reported in 2019 Japanese Yen (JPY) or US dollars (US$). The primary outcome was the incremental cost-effectiveness ratio (ICER). We assured robustness with deterministic and probabilistic sensitivity analyses.ResultsThe cost per patient for trastuzumab + chemotherapy was JPY 14.6 million (US$137,000), and their QALYs were 9.308, compared with JPY 14.2 million (US$131,000) and 9.101, respectively, for trastuzumab monotherapy. The ICER of trastuzumab + chemotherapy versus trastuzumab monotherapy was JPY 2.7 milllion/QALY (US$17,200/QALY). The ICER for trastuzumab with chemotherapy varied from "Dominant" to "Dominated" in one-way sensitivity analysis.ConclusionsThe base-case analysis suggests that AdjCT with trastuzumab + chemotherapy is likely to be a cost-effective choice for patients with HER2-positive BC aged 70 years or older. However, the sensitivity analysis suggested uncertainty regarding the cost-effectiveness of trastuzumab + chemotherapy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40261-022-01124-y.

Benefit for single-agent adjuvant chemotherapy in elderly patients with locally advanced gastric adenocarcinoma

Current NCCN guidelines exclude the possibility of using single-agent adjuvant chemotherapy in locally advanced gastric adenocarcinoma, while allowing doublet chemotherapy. However, single-agent adjuvant chemotherapy is a valid treatment option in other gastrointestinal malignancies, preferred for elderly and/or frail patients. The current study used a nationwide oncology database to assess the benefit of single-agent adjuvant chemotherapy, specifically in the elderly population. Using the National Cancer Database (2004-2016) we identified 1953 individuals with non-metastatic gastric adenocarcinoma who underwent upfront D2 gastrectomy with pathologic stage ≥ T3 or Npos and free surgical margins, and had not received either preoperative chemotherapy or pre-/postoperative radiotherapy. We used IPTW analysis to compare overall survival between individuals receiving either single- or multi-agent adjuvant chemotherapy, or referred to observation alone. Individuals receiving single-agent chemotherapy had an overall survival benefit compared with observation alone, with an HR of 0.70 (95% CI 0.55-0.88, p < 0.001). Individuals over the age of 65 had an OS benefit with an HR of 0.61 (95% CI 0.46-0.82, p < 0.001). Comparing individuals over the age of 65 receiving single- vs. multi-agent chemotherapy, there was no overall survival difference with an HR of 0.87 (95% CI 0.64-1.18, p = 0.38). Single-agent adjuvant chemotherapy with a fluoropyrimidine in locally advanced gastric adenocarcinoma following D2 gastrectomy can improve overall survival in elderly patients. Clinicians may consider using either capecitabine or 5-FU as a treatment option in the adjuvant setting for this age group.