Chemotherapy In Older Patients Research Articles

Inotuzumab Ozogamicin and Low-Intensity Chemotherapy in Older Patients With Newly Diagnosed CD22+ Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia.

The use of inotuzumab ozogamicin (InO), a conjugated anti-CD22 monoclonal antibody, is becoming a promising frontline treatment for older patients with ALL. EWALL-INO is an open-label prospective multicenter phase II trial (ClinicalTrials.gov identifier: NCT03249870). Patients age 55 years and older with newly diagnosed CD22+ Philadelphia chromosome-negative (Ph-) B-cell precursor (BCP) ALL were eligible. After a prephase, a first induction consisting of vincristine, dexamethasone, and three injections of InO (0.8 mg/m2 day 1, 0.5 mg/m2 day 8/day 15) was followed by a second induction combining cyclophosphamide, dexamethasone, and two injections of InO (0.5 mg/m2 day 1/day 8). Responders received up to six cycles of chemotherapy consolidation and 18-month chemotherapy maintenance. Allotransplant was allowed after three consolidations. The primary end point was 1-year overall survival (OS). Between December 2017 and March 2022, 131 patients (median age 68 years) were included. Three patients died during induction 1 (n = 130), two from multiple organ failure and one from hemorrhage, and none during induction 2 (n = 120). After induction 2, 90% of the patients achieved complete remission (CR) or CR with incomplete platelet recovery (CRp) and 80% had measurable residual disease (MRD2) <10-4. Among responders (n = 119), 47 relapsed and 14 died in CR/CRp. One-year OS, relapse-free survival (RFS), and cumulative incidence of relapse (CIR) rates were 73.2%, 66%, and 25%, respectively. High-risk cytogenetics and lower CD22 expression (<70%) were associated with worse OS, while both high-risk cytogenetics and MRD2 ≥10-4 were associated with lower RFS and higher CIR. The 10 allotransplanted patients had very favorable outcomes (90% 2-year OS/RFS and no relapse). Only one nonfatal sinusoidal obstructive syndrome was documented during the study. Our results support InO's use in first-line regimens for older patients with CD22+ Ph- BCP-ALL.

572P Tolerance of adjuvant chemotherapy in older patients after resection of stage III colon adenocarcinoma from PRODIGE 34 – FFCD 1402 - ADAGE randomized phase III trial

572P Tolerance of adjuvant chemotherapy in older patients after resection of stage III colon adenocarcinoma from PRODIGE 34 – FFCD 1402 - ADAGE randomized phase III trial

DOSAGE study: protocol for a phase III non-inferiority randomised trial investigating dose-reduced chemotherapy for advanced colorectal cancer in older patients

IntroductionTreating older adults with chemotherapy remains a challenge, given their under-representation in clinical trials and the lack of robust treatment guidelines for this population. Moreover, older patients, especially those with...

Prediction of moderate and severe toxicities of chemotherapy in older patients with cancer: a propensity weighted analysis of ELCAPA cohort.

Currently available predictive models for chemotherapy-related toxicity are not sufficiently discriminative in older patients with cancer and do not consider moderate toxicities. The purpose of this study was to identify factors associated with moderate and severe chemotherapy toxicities in older patients with cancer. Patients aged 70+ recruited in the prospective ELCAPA cohort were analyzed. A total of 837 patients with data on toxicities had received chemotherapy without other systemic treatment and were included between 2015 and 2022. To adjust for any imbalances in the distribution of covariates between patients receiving single-agent chemotherapy vs combination chemotherapy, we applied overlap weighting (a propensity-score-based technique). We used multinomial logistic regression. Median (interquartile range) age was 81 (77-84). Forty-one percent experienced moderate toxicity, and 33% experienced severe toxicity. Hematologic toxicities accounted for 53% of severe toxicities and 66% of moderate toxicities. Age <80 years, cancer type, metastatic status, Eastern Cooperative Oncology Group performance status (ECOG-PS) >1, no cognitive impairment were associated with combination chemotherapy decision. In a univariate analysis with overlap weighting, no factors were associated with moderate toxicity. Hemoglobin < 0g/dL and a CIRS-G score >12 were associated with severe toxicity. In a multivariate analysis, only hemoglobin < 10g/dL was independently associated with severe toxicity, adjusted OR 2.96 (95% CI, 1.20-7.29). By addressing indication bias for combination chemotherapy decision, only anemia and not cancer type, combination chemotherapy was predicting for severe chemotherapy-related toxicity in older patients with cancer. We did not find any predictors of moderate chemotherapy-related toxicity.

Abstract PS13-07: Systemic therapy in geriatric patients with triple negative breast cancer: a National Cancer Database analysis

Abstract Background Breast cancer (BC) incidence increases with age and is the leading cause of new cancer diagnosis among women in the United States. Although the median age of diagnosis is 63 years (yrs.), over a third of patients diagnosed, and about half of BC mortality in Western societies are in patients over 70 yrs. old. Overall, outcomes for early-stage BC have improved. Despite the lower incidence of triple negative BC (TNBC) (12%-15%) the 5-year survival is 8% to 16% lower than in hormone receptor-positive BC. With the improved life expectancy in the US and the increased incidence of BC as patients age, it is of vital importance to know how to treat BC in the elderly. Unfortunately, optimal management of BC among the elderly has not been adequately studied due to underrepresentation in clinical trials. Furthermore, there is limited information of the potential toxicity and real benefit of chemotherapy in older patients. Methods This is a retrospective analysis of data collected from the National Cancer Database (NCDB), a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society, during the years 2004 to 2019. All women ≥65yrs with early stage TNBC (stages I-III) were included in the analysis. Patients were categorized into three treatment groups – those who did not receive chemotherapy (No-CT), those who received chemotherapy (CT), and those who received chemotherapy and immunotherapy (CTIO). After adjusting for multiple variables including race, insurance, Charleson-Deyo score, stage at diagnosis, and receipt of loco-regional therapy, using the log rank P value, the age cutoff over which the survival rates were not significantly different between two treatment groups (No-CT and CT/CTIO) was identified. The main outcome of this study was all-cause mortality Results A total of 11,416 women with TNBC were included in the analysis. Of these, 4105 (36.0%) received No-CT, while 7311 (64.0%) received CT/CTIO. Log rank P values showed that above 81 years, there was no survival benefit between No-CT and CT/CTIO. A further analysis categorized patients into two groups – those between 65-80yrs and those ≥81 yrs. old. Cox proportional regression analysis showed that among patients between 65-80 yrs. all-cause mortality was significantly lower among patients in the CT/CTIO group compared to those in the No-CT group (hazard ratio [HR], 0.52; CI: 0.45-0.60). However, among patients ≥81yrs old, there was no significant difference in all-cause mortality between the treatment groups (hazard ratio [HR], 0.84; CI: 0.67-1.05). Conclusions: Among patients who were &amp;gt;81yrs old with early-stage TNBC, those who received treatment with CT/CTIO did not have an overall survival benefit as compared to those who received No-CT. Limitations of this study includes the small number of patients &amp;gt;81yr old who received chemotherapy which could explain why we were not able to identify a statistically significant benefit of CT/CTIO. Another limitation is that we were not able to assess breast cancer specific mortality. However, this analysis highlights the importance of individualizing treatment recommendations in older patients, who may not garner the same benefit of treatment as younger patients. Additional studies are required to clarify contributing factors and to help optimize the management of geriatric patients with TNBC. Table 1. Patient characteristics based on treatment. Citation Format: Yolcar Chamorro, Muni Rubens, Mukesh Roy, Naomi Dempsey, Reshma Mahtani, Manmeet Ahluwalia, Lauren Carcas, Ana Sandoval-Leon. Systemic therapy in geriatric patients with triple negative breast cancer: a National Cancer Database analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS13-07.

Baseline total brain volume predicts changes in quality of life and overall survival after cranial radiotherapy in older patients with glioblastoma: Results from the prospective BRITER study.

Short-course partial brain radiotherapy ± chemotherapy for older patients with GBM extends survival but there is no validated evidence for prediction of individual risk of acute radiotherapy-related side effects. This prospective multicentre observational trial recruited patients with newly diagnosed GBM aged ≥65 planned for cranial radiotherapy. Baseline MRI scans were analyzed for markers of brain resilience including relative total brain volume (ratio of cerebrospinal fluid (CSF) volume to total intracranial volume (TIV)) and their relationship to change in quality of life (QoL). 126 patients enrolled: mean age 72 years (range 65-83). 77% had debulking surgery. 79% received radiotherapy with concurrent TMZ, and 21% received palliative radiotherapy alone. The median OS was 10.7 months. After accounting for age, sex, treatment, and baseline MoCA score, there was a relationship between baseline CSF:TIV and change in QoL score at 8 weeks post treatment. For each unit point of increase in CSF:TIV, there was a corresponding decrease in QoL score of 1.72 (95% CI -3.24 to -0.19 P = .027). 35 participants were too unwell to complete questionnaires or had died by the 8 week follow-up visit. In this subgroup, post hoc logistic regression showed baseline CSF:TIV was related to the risk of non-attendance (OR 1.35, 95% CI 1.01 to 1.80, P = .042). Cox regression models showed baseline CSF:TIV was associated with worsened OS (HR 1.41, 95% CI 1.19 to 1.66, P < .001). This study provides evidence to support the use of an imaging biomarker to help assess the risk:benefit ratio for radiotherapy.

Prognostic impact of clinical factors for immune checkpoint inhibitor with or without chemotherapy in older patients with non-small cell lung cancer and PD-L1 TPS ≥ 50.

The proportion of older patients diagnosed with advanced-stage non-small cell lung cancer (NSCLC) has been increasing. Immune checkpoint inhibitor (ICI) monotherapy (MONO) and combination therapy of ICI and chemotherapy (COMBO) are standard treatments for patients with NSCLC and programmed cell death ligand-1 (PD-L1) tumor proportion scores (TPS) ≥ 50%. However, evidence from the clinical trials specifically for older patients is limited. Thus, it is unclear which older patients benefit more from COMBO than MONO. We retrospectively analyzed 199 older NSCLC patients of Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 and PD-L1 TPS ≥ 50% who were treated with MONO or COMBO. We analyzed the association between treatment outcomes and baseline patient characteristics in each group, using propensity score matching. Of the 199 patients, 131 received MONO, and 68 received COMBO. The median overall survival (OS; MONO: 25.2 vs. COMBO: 42.2 months, P = 0.116) and median progression-free survival (PFS; 10.9 vs. 11.8 months, P = 0.231) did not significantly differ between MONO and COMBO group. In the MONO group, OS was significantly shorter in patients without smoking history compared to those with smoking history [HR for smoking history against non-smoking history: 0.36 (95% CI: 0.16-0.78), P = 0.010]. In the COMBO group, OS was significantly shorter in patients with PS 1 than those with PS 0 [HR for PS 0 against PS 1: 3.84 (95% CI: 1.44-10.20), P = 0.007] and for patients with squamous cell carcinoma (SQ) compared to non-squamous cell carcinoma (non-SQ) [HR for SQ against non-SQ: 0.17 (95% CI: 0.06-0.44), P < 0.001]. For patients with ECOG PS 0 (OS: 26.1 months vs. not reached, P = 0.0031, PFS: 6.5 vs. 21.7 months, P = 0.0436) or non-SQ (OS: 23.8 months vs. not reached, P = 0.0038, PFS: 10.9 vs. 17.3 months, P = 0.0383), PFS and OS were significantly longer in the COMBO group. ECOG PS and histological type should be considered when choosing MONO or COMBO treatment in older patients with NSCLC and PD-L1 TPS ≥ 50%.

Real-world data on the first-line immune checkpoint inhibitors or in combination with chemotherapy in older patients (aged ≥ 75 years) with advanced non-small cell lung cancer

PurposeThe purpose of this study is to investigate the efficacy and safety of immune checkpoint inhibitors (ICIs) or plus with chemotherapy in older patients. MethodsWe enrolled 110 older patients with non-small cell lung cancer (NSCLC ≥75 years) who received either chemotherapy alone (chemo), ICI plus chemotherapy (ICI + chemo), or ICI alone and ICI plus other therapies, which included anti-angiogenesis drugs or other novel ICI (ICIs). Patient characteristics, treatment response, survival, and toxicity were evaluated. ResultsIn total population, the ICIs group has the highest disease control rate (DCR 75%). There were no significant differences in progression-free survival (PFS) and overall survival (OS) among older patients between ICI + chemo and ICIs groups (PFS: 5.3 months vs. 5.5 months, p = 0.70, OS: 10.7 months vs. 20.3 months, p = 0.995). Meanwhile, we observed ICIs had a longer PFS and OS than chemo group (PFS: 3.9 months vs. 5.5 months, p = 0.01, OS: 10.9 months vs. 20.3 months, p = 0.05). Subgroup analysis showed that patients with programmed death ligand-1 (PD-L1) ≥ 1% had a distinct longer trend toward OS in ICIs group compared to ICI + chemo group (22.4 months vs. 10.7 months, p = 0.605), even though there was no significant difference. In terms of safety, ICIs was more tolerable and had a lower discontinuation rate than ICI + chemo group. ConclusionIn the real world, ICI + chemo is more likely to be discontinued due to adverse effects and does not significantly improve patient survival compared with ICIs treatment in total population and subgroup. Therefore, ICI alone or ICIs plus other therapies, such as anti-angiogenesis drugs or other novel ICI (ICIs) could be recommended for older cases with PD-L1 positive NSCLC.

Real-world impact on overall survival of oxaliplatin-based adjuvant chemotherapy in older patients with colorectal cancer in Mexico.

61 Background: Colorectal cancer (CRC) is one of the most commonly diagnosed cancer both in Mexico and worldwide, with the peak incidence in patients &gt;65 years. The use of adjuvant chemotherapy (CT) improves the prognosis of high-risk CRC. The benefit from fluorouracil (FU)-based CT across all age groups is not questionable, but the use of oxaliplatin (Ox) is controversial. Methods: Original, retrospective, observational study. Included patients diagnosed with CRC adenocarcinoma treated at the Instituto Nacional de Cancerología México, between 2004 to 2022. Statistical analysis required: X2 and t-test, Kaplan Meier, Log Rank, and Cox Regression. Statistical significance differences were assessed when p was bilaterally &lt;0.05. Results: From 1,238 patients with localized CRC, 275 patients were included in analysis and divided into 2 groups: young (≤ 30 years) (n = 54), and older (≥ 70 years) (n = 221). Most patients were female for both groups (55%). Comorbidities were observed in 2% of young patients and 51% of older patients (p &lt; 0.001). Stages (S) were: II (31%; 39%), and III (59%; 47%). CT was received in 70% of young and 47% of older patients (p = 0.002). Regarding CT regimens, 56% and 21% of young and older patients respectively, had oxaliplatin (p &lt; 0.001), while 21% of young and 32% of older patients did not complete the CT (p = 0.012). Overall survival (OS) analysis was performed considering age and S. S-II median-OS was not reached (NR) for both groups, while S-III median-OS was 170 months (m) for young versus NR for older (p = 0.690). When including CT in OS analysis, patients S-II median-OS was NR for all groups (p = 0.081), while S-III median-OS was 170 m with and 19 m without CT for young versus NR with and 89 m without CT for older, respectively (p = 0.010, 95% CI 0.059-0.123). In S-III older patients, a sub-analysis was performed considering Ox: 10-year-OS was 71% versus 60% for patients treated with and without Ox respectively (p = 0.030, 95% CI 0.25-0.93). In Cox-Regression analysis for patients with clinical stage III, regimen completion (p = 0.004; HR 0.38, 95% CI 0.201-0.745) and Ox (p = 0.022; HR 0.423, 95% CI 0.203-0.881) remained as predictor factors of OS. Conclusions: There are no studies which compare the administration of CT between young and older patients or the description of these populations in Mexico. Young patients are more likely to receive CT with Ox assumingly due to the lack of comorbidities and life expectancy. The benefit of CT on OS in young patients is not in question. An increase in OS was found in older patients who received CT with Ox, but a higher percentage of treatment discontinuation secondary to toxicity. As recommended by the literature, its essential to integrate assessment in older patients to determine which patients will benefit from complete CT regimens to increase their OS, apart from their chronological age.

Association between social background and implementation of postoperative adjuvant chemotherapy for older patients undergoing curative resection of colorectal cancers, sub-analysis of the HiSCO-04 study.

Adjuvant chemotherapy is recommended following colorectal cancer resection based on risk of recurrence. In older patients, treatment decisions should consider recurrence rates and tolerability, as well as functional prognosis, residual disease, and social factors. This study aims to investigate factors, including social background, influencing implementation of postoperative adjuvant chemotherapy in older patients undergoing curative resection for colorectal cancer. This multi-institutional prospective cohort study included 15 institutions belonging to the Hiroshima Surgical study group for Clinical Oncology. We analyzed 159 older patients aged ≥ 80years, who underwent curative resection for stage III colorectal cancer between December 2013 and June 2018, as sub-analysis of the HiSCO-04 study. In total, 62 (39.0%) patients underwent postoperative adjuvant chemotherapy. Four factors were significantly associated with its implementation: performance status < 2, Charlson Comorbidity Index < 2, prognostic nutritional index ≥ 40, and presence of a spouse or siblings as lifestyle supporters. No significant difference was found in the backgrounds between complete and incomplete postoperative adjuvant chemotherapy patients. Performance status, Charlson Comorbidity Index, nutritional status, and presence of a spouse or siblings as lifestyle supporters are possible factors influencing the implementation of postoperative adjuvant chemotherapy in older patients. To select appropriate treatment options, including postoperative adjuvant chemotherapy, it is essential to consider physical condition and comorbidities of older patients, thoroughly explain the situation to their families, and establish a support system to enhance understanding of the available treatment options.

Effectiveness and safety of standard chemotherapy in older patients with ovarian cancer: a retrospective analysis by age group and treatment regimen.

To evaluate the effectiveness and safety of standard chemotherapy administered to patients >70 years with advanced ovarian cancer (OC). Medical records of 956 advanced-stage patients with OC treated between 2002-2020 with standard surgery and paclitaxel-carboplatin chemotherapy in a three-weekly (PC-3W) or weekly (PC-1W) regimen were reviewed. Treatment response and tolerability were compared between patients ≤70 years (N=723) and >70 years (N=233) with stratification to septuagenarians (>70-80 years) and octogenarians (>80 years). Median overall survival (mOS) in patients >70 was 41.26 months (95% confidence interval [Cl], 37.22-45.14) and median progression-free survival (mPFS) was 11.04 months (95% Cl, 8.97-15.74). No statistically significant differences in mPFS and mOS were observed between septuagenarians and octogenarians. Patients >70 treated with PC-1W versus PC-3W had significantly longer mOS (57.17 versus 30.00 months) and mPFS (19.09 versus 8.15 months). Toxicity rates were mostly similar between younger and older patients. Among patients >70 treated with PC-1W, the rate of neutropenia (75.7% versus 51.8%, p=0.0005), thrombocytopenia (41.0% versus 22.2%, p=0.0042) and anemia (78.1% versus 51.9%, p<0.0001) were significantly higher and the rate of grade 2 alopecia was statistically significantly lower compared with those >70 treated with PC-3W. Significantly more patients treated with PC-1W completed ≥6 chemotherapy cycles, suggesting better tolerability of this regimen. Older patients with OC may benefit from improved OS with reasonable toxicity if treated with standard chemotherapy. Older patients treated with PC-1W are more likely to complete the full chemotherapy course and survive longer compared with those treated with conventional PC-3W.

Phase 2 Trial of Mini-Hyper-CVD Plus Inotuzumab Ozogamicin, with or without Blinatumomab, in Older Patients with Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia

Background The introduction of inotuzumab ozogamicin (InO) and blinatumomab (blina) has drastically improved the overall survival (OS) of patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). Older patients with B-ALL have worse outcomes compared with younger patients due to the poor-risk biology of their disease and their inability to tolerate intensive chemotherapy. We aim to study the incorporation of InO and blina with low intensity chemotherapy in older patients with newly diagnosed (ND) B-ALL. Methods Adults ≥60 years with ND Philadelphia chromosome (Ph)-negative B-ALL who were untreated or had received up to two cycles of previous therapy were eligible. Other inclusion criteria included an Eastern Cooperative Oncology Group (ECOG) performance status of ≤3 and adequate organ function. Patients with central nervous system (CNS) disease were eligible. Patients received mini-Hyper-CVD (mHCVD, cyclophosphamide 150mg/m 2 q12h D1-3, dexamethasone 20mg daily D1-4, 11-14, and vincristine 2mg D1, 8 alternating with methotrexate (MTX) 250mg/m 2 D1 &amp; cytarabine 500mg/m 2 q12h D2, 3) for up to 8 cycles. Eight doses of intrathecal (IT) MTX /cytarabine were given for CNS prophylaxis; patients with CNS disease had IT hydrocortisone, MTX, and cytarabine twice weekly till CNS clearance, then weekly x4. Eight doses of rituximab 375mg/m 2 were given on D1, 8 of C1-4 if CD20 was ≥20% by flow cytometry. Initially, InO was given at 1.3-1.8mg/m 2 on D3 of C1 and 1.0-1.3mg/m 2 on D3 in C2-4. The protocol was amended from patient 50 such that InO was given in fractionated doses with a maximum cumulative dose of 2.7mg/m 2 (0.6 mg/m 2 on D2 of C1, 0.3 mg/m 2 on D8 of C1, then 0.3 mg/m 2 on D2 and D8 of C2-4). Ursodeoxycholic acid was given to all patients. Four cycles of blina 28µg/day replaced C5-8 of mHCVD + InO. Maintenance was initially with vincristine 2mg D1, prednisolone 50mg daily D1-5, 6-mercaptopurine 50mg BID &amp; MTX 10mg/m 2 weekly (POMP) for three years. After the protocol amendment, this was reduced to 12 cycles of POMP, with one cycle of blina given after every three POMP cycles (total four blina cycles). Results 83 patients with a median age of 68y (range, 60 - 87; ≥70y, 34%) were enrolled (Table 1). Several patients had high-risk features: 25 (39%) harbored TP53 mutations, 9 (18%) had a Ph-like signature, and 19 (23%) had high-risk cytogenetics (12 low hypodiploidy/near triploidy, 3 tetraploidy, 3 complex and 1 t(4;11)). 77 patients were not in CR at enrollment and evaluable for response. 76 (99%) responded, with 69 (90%) attaining CR. Among responders, 60 (79%) and 71 (94%) patients had no detectable minimal residual disease (MRD) by flow cytometry after C1 and overall, respectively. No early deaths were observed. After a median follow-up of 88 months (IQR, 41-120), the median overall survival (OS) was 56 months (95%CI, 28-85), and the median progression-free survival (PFS) was 47 months (95% CI, 21-72). The 5-year continuous remission duration (CRD) and OS rates were 78% and 49%, respectively. The 5-year OS for patients aged 60-69 without adverse cytogenetics (n=40), age 60-69 with adverse cytogenetics (n=15), age ≥70 without adverse cytogenetics (n=24) and age ≥70 with adverse cytogenetics (n=4) were 73%, 27%, 39% and 0%, respectively. Five (6%) patients underwent allogeneic stem cell transplantation (ASCT) in first CR, 12 (15%) relapsed, 33 (40%) remain in ongoing continuous remission without ASCT, and 33 (40%) died in remission. Of the 12 relapsing patients, 5 had extramedullary disease, all with CNS involvement. 12 (14%) patients died due to progressive disease at a median of 23 (range 2 - 78) months; these patients had a median age of 64 (range 60 - 79) years. Of the 33 who died in remission, nine were due to secondary myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The median age of these patients was 71 years (range, 64 - 87), with a median time to MDS/AML of 34 months (range, 7 - 75). Fourteen deaths in CR were due to treatment-related complications (9 sepsis, 3 veno-occlusive disease (VOD), 2 ASCT). Six (7%) patients developed veno-occlusive disease, 4/49 (8%) in the pre-amendment group and 2/34 (6%) in the post-amendment group. Conclusion Older patients with ND Ph-negative ALL treated with mHCVD plus InO, with or without blina had excellent response rates and deep remissions. However, further adjustment of the regimen is needed, especially in patients ≥70 years.

SIOG2023-4-P-282 - The relation between CARG score and the starting dose of chemotherapy in older patients

SIOG2023-4-P-282 - The relation between CARG score and the starting dose of chemotherapy in older patients

SIOG2023-5-P-370 - Variables related with sarcopenia and risk of severe toxicity of chemotherapy in older patients

SIOG2023-5-P-370 - Variables related with sarcopenia and risk of severe toxicity of chemotherapy in older patients

Indications for neoadjuvant chemotherapy in older patients undergoing esophagectomy for esophageal cancer.

To investigate the indications for neoadjuvant chemotherapy (NAC) in esophageal cancer patients aged 75years or older. We analyzed data, retrospectively, from 155 patients over 75years old, who underwent esophagectomy for esophageal cancer between 2010 and 2020. Forty-one patients underwent upfront surgery (US group) and 114 were treated with NAC followed by surgery (NAC group). We compared the patient backgrounds and perioperative outcomes including prognosis, between the two groups. The NAC group patients were significantly younger and had significantly more advanced clinical stage disease than the US group patients. The incidence of postoperative complications was similar in the two groups. Patients with a good pathological response to NAC had a significantly better prognosis than those with a poor response and those in the US group. Among patients with a performance status (PS) of 0, the 5-year OS rate was 56.5% in the NAC group and 38.1% in the US group (HR = 0.63, 95% CI 0.35-1.12). Among those with a PS of 1-2, the 5-year OS rates were 28.1% and 57.1%, respectively (HR = 1.69, 95% CI 0.99-2.89; P = 0.037 for interaction). NAC did not improve the postoperative prognosis of older esophageal cancer patients with a PS of 1 or higher.

10-day decitabine versus 3 + 7 chemotherapy followed by allografting in older patients with acute myeloid leukaemia: an open-label, randomised, controlled, phase 3 trial

Many older patients with acute myeloid leukaemia die or cannot undergo allogeneic haematopoietic stem-cell transplantation (HSCT) due to toxicity caused by intensive chemotherapy. We hypothesised that replacing intensive chemotherapy with decitabine monotherapy could improve outcomes. This open-label, randomised, controlled, phase 3 trial was conducted at 54 hospitals in nine European countries. Patients aged 60 years and older who were newly diagnosed with acute myeloid leukaemia and had not yet been treated were enrolled if they had an Eastern Cooperative Oncology Group performance status of 2 or less and were eligible for intensive chemotherapy. Patients were randomly assigned (1:1) to receive decitabine or standard chemotherapy (known as 3 + 7). For the decitabine group, decitabine (20 mg/m2) was administered for the first 10 days in the first 28-day cycle, followed by 28-day cycles consisting of 5 days or 10 days of decitabine. For the 3 + 7 group, daunorubicin (60 mg/m2) was administered over the first 3 days and cytarabine (200 mg/m2) over the first 7 days, followed by 1-3 additional chemotherapy cycles. Allogeneic HSCT was strongly encouraged. Overall survival in the intention-to-treat population was the primary endpoint. Safety was assessed in all patients who received the allocated treatment. This trial is registered at ClinicalTrials.gov, NCT02172872, and is closed to new participants. Between Dec 1, 2014, and Aug 20, 2019, 606 patients were randomly assigned to the decitabine (n=303) or 3 + 7 (n=303) group. Following an interim analysis which showed futility, the IDMC recommended on May 22, 2019, that the study continued as planned considering the risks and benefits for the patients participating in the study. The cutoff date for the final analysis presented here was June 30, 2021. At a median follow-up of 4·0 years (IQR 2·9-4·8), 4-year overall survival was 26% (95% CI 21-32) in the decitabine group versus 30% (24-35) in the 3 + 7 group (hazard ratio for death 1·04 [95% CI 0·86-1·26]; p=0·68). Rates of on-protocol allogeneic HSCT were similar between groups (122 [40%] of 303 patients for decitabine and 118 [39%] of 303 patients for 3+7). Rates of grade 3-5 adverse events were 254 (84%) of 302 patients in the decitabine group and 279 (94%) of 298 patients in the 3 + 7 group. The rates of grade 3-5 infections (41% [125 of 302] vs 53% [158 of 298]), oral mucositis (2% [seven of 302] vs 10% [31 of 298]) and diarrhoea (1% [three of 302] vs 8% [24 of 298]) were lower in the decitabine group than in the 3 + 7 group. Treatment-related deaths were reported for 12% (35 of 302) of patients in the decitabine group and 14% (41 of 298) in the 3 + 7 group. 10-day decitabine did not improve overall survival but showed a better safety profile compared with 3 + 7 chemotherapy in older patients with acute myeloid leukaemia eligible for intensive chemotherapy. Decitabine could be considered a better-tolerated and sufficiently efficacious alternative to 3 + 7 induction in fit older patients with acute myeloid leukaemia without favourable genetics. Janssen Pharmaceuticals.

Real-World Survival of First-Line Immune Checkpoint Inhibitor Treatment Versus Chemotherapy in Older Patients With Non-Small-Cell Lung Cancer and Synchronous Brain Metastases.

This study assessed real-world survival among older patients with non-small-cell lung cancer (NSCLC) and brain metastases (BMs) at diagnosis (synchronous BM [SBM]) receiving first-line immune checkpoint inhibitors (ICIs) compared with chemotherapy only. Patients with NSCLC and SBM age 65 years or older at diagnosis from 2010 to 2019 SEER-Medicare database and received US Food and Drug Administration-approved ICIs (pembrolizumab/nivolumab/ipilimumab/atezolizumab/durvalumab/cemiplimab) and/or chemotherapy (platinum-based doublets/taxane/pemetrexed/gemcitabine) as first-line systemic treatment were included, excluding those with no cranial radiation or ever being treated with targeted therapies. Overall survival time was from the start of systemic treatment (ICI/chemotherapy) to death, censored at disenrollment from Medicare part A/B, enrollment in part C, or end of the study period (December 31, 2019). Kaplan-Meier (KM) survival curves were compared between treatment groups using the log-rank test. Multivariable Cox proportional hazards (CPH) model was used to estimate hazard ratio (HR) between groups, adjusting for patients' sociodemographic and clinical characteristics. The study included 1,481 patients (1,303 chemotherapy and 178 ICI). The median (range) age was 71 (65-91) years. First-line ICI patients were more likely to be older, live in urban areas, and less likely to be non-White than the chemotherapy group. KM estimates showed that survival curves initially overlapped but diverged approximately 6 months after initiating first-line systemic treatment (median survival [95% CI]: ICI, 190 [131 to 303] days versus chemotherapy, 189 [177 to 201] days), with ICI showing a better survival than the chemotherapy group (log-rank test P < .0001). First-line ICI was associated with a lower risk of death compared with chemotherapy in adjusted CPH model (HR [95% CI], 0.67 [0.55 to 0.80]; P < .0001). Among older patients with NSCLC and SBM, first-line ICI use was associated with improved survival occurring 6 months after treatment initiation compared with chemotherapy only.

The efficacy of adjuvant chemotherapy for older adults with stage II/III gastric cancer: a retrospective cohort study

BackgroundAdjuvant chemotherapy is recommended as the standard treatment for patients with stage II/III resected gastric cancer. However, it is unclear whether older patients also benefit from an adjuvant chemotherapy strategy. This study aimed to investigate the clinical impact of adjuvant chemotherapy in older patients with stage II/III gastric cancer.MethodsThis retrospective, real-world study analyzed 404 patients with stage II/III gastric cancer visited at our institute between January 2009 and December 2019. The clinical characteristics and outcomes of patients aged 70 years or older who received adjuvant chemotherapy were compared with those who did not receive this type of treatment. Propensity score analysis was performed to mitigate selection bias.ResultsOf the 404 patients analyzed, 179 were aged 70 years or older. Fewer older patients received adjuvant chemotherapy than did younger patients (60.9% vs. 94.7%, respectively; P < 0.001). Among patients aged 70 years or older, those who received adjuvant chemotherapy had improved disease-free survival (DFS) (5-year DFS rate, 53.1% vs. 30.4%; P < 0.001) and overall survival (OS) (5-year OS rate, 68.7% vs. 52.1%; P = 0.002) compared to those who did not receive adjuvant chemotherapy. A similar survival benefit was observed in the propensity-matched cohort. Multivariate analysis showed that more advanced stage was associated with poorer OS. Receipt of adjuvant chemotherapy was independently associated with a decreased hazard of death (hazard ratio (HR), 0.37; 95% confidence intervals (CI), 0.20–0.68; P = 0.002).ConclusionsAdjuvant chemotherapy may benefit older stage II/III gastric cancer patients aged ≥ 70 years. Further prospective studies are needed to confirm these findings.

Preoperative low skeletal muscle volume can result in insufficient administration of S-1 adjuvant chemotherapy in older patients with stage II/III gastric cancer.

Older patients are more likely to encounter difficulties receiving chemotherapy, but the factors involved in the continuation of chemotherapy in these patients remain unclear. We investigated the importance of muscle mass as a factor involved in delivering a sufficient dose of postoperative S-1 adjuvant chemotherapy (ACT) to older patients with gastric cancer. The subjects of this study were 79 patients aged ≥ 65years with stage II/III gastric adenocarcinoma, who underwent curative gastrectomy and received S-1 ACT. The overall median relative dose intensity (RDI) was 75.0% (18.8-93.5%). Patients were divided into two groups for receiver operating characteristic analysis according to the cutoff value. Significantly more patients in the high skeletal muscle index (SMI) group achieved > 62% RDI of S-1 ACT (p = 0.03). Conversely, more patients in the low SMI group suffered from S-1-induced nausea (p = 0.03) and discontinued chemotherapy because of adverse events (p = 0.02). Multivariate analysis identified low SMI as an independent factor for insufficient S-1 dose delivery (p = 0.03, hazard ratio = 2.87). Preoperative SMI is an indicator of the low-dose intensity of S-1 ACT in older patients following curative gastrectomy.

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.