First-line Treatment In Older Patients Research Articles

533P First-line treatment in older patients with metastatic colorectal cancer: A large real-world study

533P First-line treatment in older patients with metastatic colorectal cancer: A large real-world study

Abstract RF02-04: A phase III study comparing trastuzumab emtansine with trastuzumab, pertuzumab, and docetaxel in older patients with metastatic HER2-positive breast cancer. (JCOG1607 HERB TEA study)

Abstract Background A combination of trastuzumab, pertuzumab, and docetaxel (HPD) is recommended as first-line treatment for patients with HER2-positive metastatic breast cancer. For older patients, it is difficult to maintain a relative dose intensity, which often impairs their quality of life. A new standard treatment option for older patients is required with less toxicity and non-inferior efficacy compared to HPD. Methods The eligibility criteria were as follows: age 65 years and older, HER2-positive metastatic breast cancer, no previous systemic treatment with chemotherapy and anti-HER2 targeted drugs, ECOG PS 0–2 for 65–74 years or 0–1 for 75 years or older, and adequate organ function. Treatment consisted of trastuzumab emtansine (T-DM1) 3.6 mg/kg every 3 weeks or HPD (trastuzumab 8 mg/kg, then 6 mg/kg, pertuzumab 840 mg, then 420 mg/body, and docetaxel 60 mg/m2, could be escalated to 75 mg/m2 if there were no unmanageable toxicity) every 3 weeks after a 1:1 ratio randomization. The trial was designed to achieve 70% power to confirm the non-inferiority of T-DM1 to HPD at a one-sided alpha of 5% with a non-inferiority margin of 1.35 in terms of the hazard ratio (HR) for overall survival (OS) as the primary endpoint. With a median OS of 30 months in both arms, 6.5 years of accrual, and 5 years of follow-up, the planned sample size was 250. Secondary endpoints were progression-free survival (PFS), response rate (RR), adverse events, cumulative breast cancer-specific mortality (BCSM), safety, and deterioration of activities of daily living. (Clinical Trial Information: UMIN000030783). Results In total, 148 patients were enrolled between January 2018 and March 2023. A total of 135 patients were assessed in the preplanned first interim analysis. The median patient age was 72 years (range 65-88) in the T-DM1 arm and 71 (65-84) in the HPD arm. The proportion of estrogen receptor-positive (10%) patients was well balanced between both arms (49.3 and 55.6%, respectively). Of these patients, 64.8% had stage IV disease and 35.2% had recurrent disease. T-DM1 was not non-inferior to HPD (HR 1.487; 99.9% CI, 0.288 to 7.678) in terms of OS. The median PFS was 9.8 months in the T-DM1 arm and 18.4 months in the HPD arm (HR 1.749; 95%CI, 1.124-2.723). Response rates were lower in the T-DM1 arm than that of the HPD arm (52.7% [95% CI, 38.8-66.4] and 76.8% [95% CI, 63.6-87.0], respectively) (p=0.099). BCSM was higher in the T-DM1 arm than that of the HPD arm (HR 1.617; 95% CI, 0.764-3.425). Grade 3 and higher neutropenia were less common in the T-DM1 arm than in the HPD arm (0 vs. 30.4%); however, thrombocytopenia was more common in the T-DM1 arm than in the HPD arm (16.9 vs. 0%). Grade 3 or more non-hematological adverse events were less common and lower in the T-DM1 arm (35.2%) than in the HPD arm (58.6%), including fatigue (5.6% vs. 22.9%), diarrhea (0% vs. 11.4%), appetite loss (8.5% vs. 11.4%), and febrile neutropenia (0% vs. 10.0%), which reduced the quality of life in older patients with HER2-positive metastatic breast cancer. Conclusion T-DM1 was not non-inferior to HPD in terms of OS. However, T-DM1 showed better tolerability in terms of frequency and severity of adverse events. HPD will continue to be the standard of care as the first-line treatment for older patients with HER2-positive metastatic breast cancer. Older patients with breast cancer have heterogeneous health conditions. A subset analysis according to age or geriatric assessment may identify the subpopulation of older patients with HER2-positive metastatic breast cancer for whom T-DM1 is an optional treatment. Citation Format: Akihiko Shimomura, Kenji Tamura, Keita Sasaki, Ryo Sadate, Akihiko Suto, Masataka Sawaki, Naohito Yamamoto, Tomoyuki Yoshiyama, Takako Hayashi, Eriko Tokunaga, Takashi Yamanaka, Chikako Shimizu, Tadahiko Shien, Hiroji Iwata. A phase III study comparing trastuzumab emtansine with trastuzumab, pertuzumab, and docetaxel in older patients with metastatic HER2-positive breast cancer. (JCOG1607 HERB TEA study) [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 RF02-04.

Geriatric Assessment of Older Patients Receiving Trabectedin in First-Line Treatment for Advanced Soft Tissue Sarcomas: The E-TRAB Study from The German Interdisciplinary Sarcoma Group (GISG-13)

E-TRAB was a non-interventional, prospective trial investigating the feasibility and predictive value of geriatric assessments (GA) in older STS patients treated with trabectedin as first-line therapy. Primary endpoints were overall survival (OS), quality of life and individual clinical benefit assessed by the patient-reported outcome measures QLQ-C30 and PRO-CTCAE. Further, several GA tools were applied and correlated with clinical outcomes and treatment-related toxicities. The final analyses included 69 patients from 12 German-speaking sites. The median age of patients was 78 years (range: 55 to 88). Baseline data on PROs and GA identified a diverse population of older patients with respect to their global health status, although a large proportion of them suffered from limitations, required geriatric help and had a high risk of morbidity. The Cancer and Age Research Group (CARG) score classified 38%, 29% and 23% of the patients with low, intermediate and high risks for therapy-related side effects, respectively. Median OS was 11.2 months [95%CI: 5.6; 19.4]. The study confirmed that trabectedin as first-line treatment in older patients with STS has an acceptable and manageable safety profile. Potential prognostic factors for clinical outcome and therapy-related toxicity were identified among the GA tools. Long Timed Up and Go (TUG) showed a significant correlation to OS and early death, whereas a high CARG score (>9) was associated with an increase in unplanned hospitalizations and the incidence of toxicities grade ≥ 3.

Phase II study of S-1 plus docetaxel as first-line treatment for older patients with advanced gastric cancer (OGSG 0902).

Although there is insufficient evidence for the treatment of older patients with advanced gastric cancer, fluorouracil combined with platinum chemotherapy has been recognized as a standard first-line treatment for such populations in Japan despite the lack of efficacy and toxicity data. Patients aged 75years or older with advanced gastric cancer were enrolled. S-1 plus docetaxel (docetaxel: 40mg/m2, day 1; S-1: 80mg/m2, days 1-14; q21 days) was repeated every 3weeks. The primary endpoint was overall response rate. Secondary endpoints were safety, progression-free survival, time to treatment failure, and overall survival. The sample size was calculated as 30 under the hypothesis of an expected response rate of 40% and a threshold response rate of 20%, at a power of 90% and a two-sided alpha value of 5%. From February 2010 to January 2015, 31 patients were enrolled and assessed for efficacy and toxicity. The response rate was 45.2% (95% CI 27.3%-64.0%; p = 0.001) and it exceeded the expected response rate set at 40%. Median progression-free survival was 5.8months, the 1-year survival rate was 58.1%, and the median survival time was 16.1months. The major grade 3/4 adverse events were neutropenia (58%), febrile neutropenia (13%), anemia (10%), anorexia (10%), and fatigue (6%). These findings indicate that S-1 plus docetaxel as first-line treatment for older patients is feasible and that it has promising efficacy against advanced gastric cancer.

Cost-Effectiveness of Ibrutinib as First-line Treatment for Older Patients With Chronic Lymphocytic Leukemia in Iran

ObjectivesWe aimed to evaluate the cost-effectiveness of ibrutinib versus chemoimmunotherapy for frontline treatment of elderly patients with chronic lymphocytic leukemia in Iran. MethodsWe developed a partitioned survival model with 3 health states (progression-free survival, post-progression survival, and death) and a lifetime horizon. State memberships were determined by parametric survival analysis of the ALLIANCE (A041202) randomized controlled trial’s results, comparing first-line ibrutinib with bendamustine plus rituximab. Direct medical costs were calculated from an Iranian health system perspective. Utility values were extracted from the literature to calculate the incremental costs and quality-adjusted life-years (QALYs) associated with each strategy. To address parameter uncertainties, deterministic and probabilistic sensitivity analyses were also performed. ResultsIn the base-case analysis, ibrutinib and bendamustine plus rituximab were associated with $3739.72 and $3991.20 costs per patient as the first-line treatment strategy, respectively. They resulted in an average of 2.86 and 2.66 QALYs per patient. Thus, first-line ibrutinib was associated with 0.20 incremental QALY and $251.48 cost-saving per patient and was therefore the “dominant” strategy. In deterministic sensitivity analysis, drug prices were the key drivers of model outputs. However, none of the resulting incremental cost-effectiveness ratios exceeded the currently accepted threshold by the Iranian Food and Drug Administration ($1550 per QALY). In probabilistic sensitivity analysis, 63.3% of iterations were cost-saving and 77.4% were cost-effective. ConclusionsOur findings suggest that ibrutinib as a first-line treatment appears to be the dominant strategy, compared with the standard of care, for unselected older adults with chronic lymphocytic leukemia in Iran.

First-Line Treatment of Older Patients with CLL: A New Approach in the Chemo-Free Era.

Bruton tyrosine kinase inhibitors (BTKi) and the BCL2 inhibitor venetoclax, with or without the anti-CD20 monoclonal antibody Obinutuzumab, represent the preferred options for the first-line therapy of CLL because they are more effective and may improve quality of life. However, patient inclusion criteria are heterogeneous across trials designed for older patients, and the identification of CLL-specific parameters identifying unfit patients at risk of developing drug-specific adverse events is required to guide treatment choice. Due to inclusion/exclusion criteria in trials, higher discontinuation rates with BTKi were reported in real-world studies, and registry analyses provided useful information on factors predicting earlier discontinuation in a real-world setting. Though targeted agents were shown to be cost-effective treatments in high-income countries, the out-of-pocket expenses may limit accessibility to these drugs, and the overall expenditure for new drugs in CLL is projected to increase substantially, posing an issue for sustainability. This being said, the choice of a finite-duration treatment based on venetoclax-containing regimens or treatment until progression with BTKi is today possible in high-income countries, and the therapy choice drivers are represented by coexisting medical conditions rather than age, patient expectations, logistics, and sustainability.

Venetoclax combined with low dose cytarabine compared to standard of care intensive chemotherapy for the treatment of favourable risk adult acute myeloid leukaemia (VICTOR): Study protocol for an international, open-label, multicentre, molecularly-guided randomised, phase II trial

BackgroundFor patients with acute myeloid leukaemia (AML), the only potentially curative treatment is intensive chemotherapy (IC). This is highly toxic, particularly for patients > 60 years, potentially leading to prolonged hospitalisations requiring intensive supportive care, and sometimes treatment-related death. This also results in extensive healthcare costs and negatively impacts quality of life (QoL). Venetoclax with low-dose cytarabine (VEN + LDAC) is a novel, low-intensity treatment for AML patients who cannot receive IC. VEN + LDAC is given as an outpatient and toxicity appears significantly lower than with IC. Analysis of clinical trials performed to date are promising for patients with the genotype NPM1mutFLT3 ITDneg, where remission and survival rates appear comparable to those achieved with IC.MethodsVICTOR is an international, two-arm, open-label, multi-centre, non-inferiority, randomised-controlled phase II trial to assess VEN + LDAC compared to standard of care (IC) as first-line treatment in older patients (initially aged ≥ 60 years) with newly diagnosed AML. The trial will recruit patients with a NPM1mutFLT3 ITDneg genotype; those with a favourable risk in relation to the experimental treatment. University of Birmingham is the UK co-ordinating centre, with national hubs in Aarhus University Hospital, Denmark, and Auckland District Health Board, New Zealand. The primary outcome is molecular event-free survival time where an event is defined as failure to achieve morphological complete response (CR) or CR with incomplete blood count recovery after two cycles of therapy; molecular persistence, progression or relapse requiring treatment change; morphological relapse, or; death. Secondary outcomes include cumulative resource use at 12- and 24-months, and QoL as assessed by EORTCQLQ-C30 and EQ-5D-3L at 3-, 6-, 12-, 18- and 24-months. The trial employs an innovative Bayesian design with target sample size of 156 patients aged > 60 years.DiscussionThe principle underpinning the VICTOR trial is that the chance of cure for patients in the experimental arm should not be compromised, therefore, an adaptive design with regular checks on accumulating data has been employed, which will allow for a staged expansion of the trial population to include younger patients if, and when, there is sufficient evidence of non-inferiority in older patients.Trial registrationEudraCT: 2020–000,273-24; 21-Aug-2020.ISRCTN: 15,567,173; 08-Dec-2020.

Eribulin as first-line treatment in older patients with advanced breast cancer: A multicenter phase II trial [SAKK 25/14]

IntroductionStandard-dose eribulin mesylate (1.4 mg/m2 d1 + 8) achieves clinical benefit rates of 26%–52% in patients with metastatic breast cancer (mBC). <10% of patients in the registration trial were ≥ 70 years old; dose reductions were common in these older patients. Materials and MethodsThis single-arm phase II trial explored the efficacy of reduced starting dosing of first-line eribulin at 1 mg/m2 d1 + 8 q3 weeks in patients with mBC aged ≥70 years. The primary endpoint was a disease control rate (DCR) ≥55%. The secondary endpoints were objective response (OR), progression-free survival (PFS), overall survival (OS), and patient-reported neurotoxicity. ResultsOverall, 77 patients were accrued; their median age was 76 years and Eastern Cooperative Oncology Group performance status was 0–1 in 90%. The DCR was 40% (90% confidence interval [CI]: 31–50); therefore, the primary endpoint was not reached. The overall response rate was 22% (95%CI: 13–33), median PFS 5.4 months (95%CI: 4.5–7.7), and median OS 16.1 months (95%CI: 13.5–26.9). Dose modifications were necessary in 35% of patients. In nine patients, more than fifteen cycles were given; 48 patients (62%) experienced at least one grade 3 toxicity. Median patient-reported neurotoxicity scores remained stable for at least fifteen cycles. The main reason for treatment discontinuation was disease progression (57%). DiscussionWe report the first prospective data on first-line eribulin in older patients. The reduced starting dose of 1.1 mg/m2 was safe, with prolonged treatment and DC achieved in a considerable proportion of patients (but less than the 55% assumed), without cumulative neurotoxicity. The reduced dose was apparently within the range of the minimal effective dose, as shown by the efficacy lack in patients requiring further dose reductions. Thus, our results do not support the approach of a reduced starting dose for older patients.

Effect of Refined Perioperative Nursing on the Efficacy of Noninvasive Ventilation in Elderly Patients with Lung Cancer and Respiratory Failure.

NIV (noninvasive ventilation) is becoming more popular as a first-line treatment for older patients with lung cancer who are experiencing acute respiratory failure. In the ICU, older age is linked to worse results with mechanical breathing. When dealing with severely sick patients, noninvasive ventilation is beneficial. Due to the risk of NIV failure and the higher mortality induced by delayed intubation, it is difficult to apply to older patients, especially those with lung cancer and respiratory insufficiency. As a result, for a successful outcome, nurse interventions should be provided to patients during noninvasive ventilation. This paper proposes the application of integrated perioperative nursing models on the elderly patients with lung cancer and respiratory failure. We have applied three nursing models: peer support nursing model, multidisciplinary cooperative nursing model, and transcultural nursing theory. The effect of the proposed nursing model on the efficacy of NIV is evaluated using the Logical Decision Tree Regression (LDTR) model. It is optimized using Iterative Fruit Fly Optimization Algorithm (IFOA). The performance of the suggested system is analysed, and it is observed that the patients showed better surgical outcomes when provided with the integrated nursing models.

Primary results from the double-blind, placebo-controlled, phase III SHINE study of ibrutinib in combination with bendamustine-rituximab (BR) and R maintenance as a first-line treatment for older patients with mantle cell lymphoma (MCL).

LBA7502 Background: Elderly patients (pts) with MCL are unsuitable for intensive chemotherapy or transplantation due to excessive toxicities. Single-agent ibrutinib (Ibr), a first-in-class, oral Bruton’s tyrosine kinase inhibitor (BTKi), has transformed the care of pts with relapsed or refractory MCL with durable activity. We conducted a phase III trial (SHINE; NCT01776840) to evaluate combining Ibr with a standard chemoimmunotherapy (BR) and R maintenance in older pts with untreated MCL. Methods: Pts aged ≥ 65 years, enrolled between May 2013 and November 2014 from 183 sites across all geographical regions, were stratified by simplified MIPI score (low vs intermediate vs high risk) and were randomized 1:1 to Ibr (560 mg orally daily) or placebo (Pbo), plus 6 cycles of B (90 mg/m2) and R (375 mg/m2). Pts who achieved an objective response received R maintenance, administered every 8 weeks for up to 12 additional doses in both arms. Ibr and Pbo were administered until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) assessed by the investigators. Results: A total of 523 pts were randomized to Ibr + BR (n = 261) or Pbo + BR (n = 262). Median age was 71 years (range, 65–87), 65.6% of pts had low/intermediate simplified MIPI, and 8.6% had blastoid/pleiomorphic histology. At the primary analysis, median follow up was 84.7 months. The primary endpoint was met as PFS was significantly improved in the Ibr arm vs the Pbo arm (hazard ratio, 0.75; one-sided P = 0.011). Median PFS was 80.6 months with Ibr in combination with BR and R maintenance, a 50% improvement over Pbo in combination with BR and R maintenance (median PFS of 52.9 months). The complete response rate was 65.5% in the Ibr arm and 57.6% in the Pbo arm ( P = 0.0567). There was no difference in overall survival between treatment arms ( P = 0.648). Time to next treatment was longer in the Ibr arm compared with the Pbo arm ( P &lt; 0.001). Fifty-two (19.9%) and 106 (40.5%) pts received subsequent anti-lymphoma therapy in the Ibr and Pbo arms, respectively; 41/106 (38.7%) received a second-line BTKi in the Pbo arm. Rates of grade 3 or 4 treatment-emergent adverse events were 81.5% and 77.3% in the Ibr and Pbo arms, respectively. Of adverse events of clinical interest for BTKis, atrial fibrillation was reported in 13.9% and 6.5% of pts in the Ibr and Pbo arms, respectively. Rates of major hemorrhage, hypertension, arthralgia, and secondary primary malignancies were similar in both arms. Quality of life was also similar in both arms. Conclusions: This phase III study in untreated MCL demonstrated that Ibr combined with BR and R maintenance significantly improved PFS compared with standard chemoimmunotherapy, with a median PFS of 6.7 years. The safety profile was consistent with the known profiles of the individual drugs. Clinical trial information: NCT01776840.

Targeted Therapy for Older Patients with Non-Small Cell Lung Cancer: Systematic Review and Guidelines from the French Society of Geriatric Oncology (SoFOG) and the French-Language Society of Pulmonology (SPLF)/French-Language Oncology Group (GOLF).

Simple SummaryTargeted therapy has become essential in the treatment of non-small cell lung cancer (NSCLC). There are currently no guidelines for older patients who are frailer with regard to this type of treatment. Two learned societies, the French Society of Geriatric Oncology (SoFOG) and the French-language Society of Pulmonology (SPLF)/French-language Oncology Group (GOLF), joined forces to conduct a systematic review of the literature from May 2010 to May 2021 regarding the efficacy, toxicity, and feasibility of targeted therapy in older patients with NSCLC. Guidelines were then drawn up to enable clinicians to adapt the type of targeted therapy proposed according to the oncological and geriatric profile of the older patient with NSCLC.Systematic molecular profiling and targeted therapy (TKI) have changed the face of Non-Small Cell Lung Cancer (NSCLC) treatment. However, there are no specific recommendations to address the prescription of TKI for older patients. A multidisciplinary task force from the French Society of Geriatric Oncology (SoFOG) and the French Society of Pulmonology/Oncology Group (SPLF/GOLF) conducted a systematic review from May 2010 to May 2021. Protocol registered in Prospero under number CRD42021224103. Three key questions were selected for older patients with NSCLC: (1) to whom TKI can be proposed, (2) for whom monotherapy should be favored, and (3) to whom a combination of TKI can be proposed. Among the 534 references isolated, 52 were included for the guidelines. The expert panel analysis concluded: (1) osimertinib 80 mg/day is recommended as a first-line treatment for older patients with the EGFR mutation; (2) full-dose first generation TKI, such as erlotinib or gefitinib, is feasible; (3) ALK and ROS1 rearrangement studies including older patients were too scarce to conclude on any definitive recommendations; and (4) given the actual data, TKI should be prescribed as monotherapy. Malnutrition, functional decline, and the number of comorbidities should be assessed primarily before TKI initiation.

Analysis of first-line treatment in older patients with metastasic colorectal cancer.

The purpose of this study was to analyse the effectiveness and safety of first-line treatment of metastatic colorectal cancer (CRCm) in older patients treated in a tertiary hospital. This was an observational and retrospective study, including patients aged 75 years or older, with CRCm, who received chemotherapy treatment in 2017. The main variables studied were type of treatment, Progression-Free Survival (PFS), Overall Survival (OS), dose reductions, and treatment delays due to adverse events. A total of 59 patients (71.2% men) with a median age of 76 years were enrolled in this study. About 70% presented colon cancer, with the left colon being the most frequent location. They were treated with 9 different schemes, in most cases using polychemotherapy and biological agents. The median PFS and OS was 12 and 30 months, respectively. A total of 23/59 of patients started treatment at doses lower than recommended in the clinical practice guidelines. In terms of safety, 34/59 of patients had at least one dose reduction, and 30/59 suffered one treatment delay. The most frequent adverse reactions were asthenia, peripheral neuropathy, diarrhoea, and palmoplantar erythrodysesthesia. Our patients presented baseline clinical characteristics similar to the general adult population, with no tumour characteristics associated with advanced age. The efficacy and toxicity were similar to those in the clinical trials, although our patients had more dose reductions. Considering the heterogeneity of patients and in the absence of clinical trials in the older population, real-life studies can be very useful.

Outcomes of decitabine treatment for newly diagnosed acute myeloid leukemia in older adults​.

We evaluated the outcomes of decitabine as first-line treatment in older patients with acute myeloid leukemia (AML) and investigated the predictors, including a baseline mini nutritional assessment short form (MNA-SF) score, of response and survival. Between 2010 and 2018, 96 AML patients aged 65 and above who received decitabine treatment at 6 centers in Korea were retrospectively evaluated. Response rates, hematologic improvements (HI), progression-free survival (PFS), and overall survival (OS) were analyzed. The median age at diagnosis was 73.9 years, and the median number of decitabine treatments administered to the patients was 4 (range, 1-29). Of 85 patients, 15 patients (17.6%) achieved complete remission (CR) or CR with incomplete blood count recovery. Twelve patients (14.1%) showed partial remission (PR), and 18 (21.2%) demonstrated HI without an objective response. The median PFS and OS were 7.0 (95% confidence interval [CI], 4.9-9.0) and 10.6 (95% CI, 7.7-13.5%) months, respectively. In multivariate analyses, MNA-SF score ≥ 8 and the absence of peripheral blood (PB) blasts were significant predictors for improved PFS and OS. For older patients with newly diagnosed AML, a high MNA-SF score and the absence of PB blasts were independently associated with improved survival.

First-line treatment in older patients with Hodgkin lymphoma: a Surveillance, Epidemiology, and End Results (SEER)-Medicare population-based study.

While Hodgkin lymphoma (HL) is highly curable in younger patients, older patients have higher relapse and death rates, which may reflect age-related factors, distinct disease biology and/or treatment decisions. We described the association between patient, disease and geographic factors and first-line treatment in older patients (≥65years) with incident HL using Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 1999 to 2014 (n=2825). First-line treatment initiated at ≤4months after diagnosis was categorised as: full chemotherapy regimen (n=699, 24·7%); partial chemotherapy regimen (n=1016, 36·0%); single chemotherapy agent or radiotherapy (n=382, 13·5%); and no treatment (n=728, 25·8%). Among the fully treated, ABVD [doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine]/AVD was most common (n=635, 90·8%). Adjusted multinomial logistic regression identified factors associated with treatment. Older age, Medicaid dual eligibility, not married, frailty, cardiac comorbidity, prior cancer, earlier diagnosis date, histology, advanced disease Stage, B symptoms and South region were independently associated with increased odds of not receiving full chemotherapy regimens. In conclusion, we found variability in first-line HL treatment for older patients. Treatment differences by Medicaid and region may indicate disparities. Even after adjusting for frailty and cardiac comorbidity, age was associated with treatment, suggesting factors such as end-of-life care or shared decision-making may influence treatment in older patients.

Treatment with Full Chemotherapy Regimens in Older Adults with Hodgkin Lymphoma Improves 3-Year Overall Survival, but Less Than Half Receive Full Regimens

Introduction Older adults with Hodgkin Lymphoma (HL) have markedly poorer outcomes than younger counterparts. This may reflect treatment decisions, age-related factors, and/or disease biology. For younger patients, standard first-line treatment typically consists of dose-dense, multi-agent chemotherapy regimens with or without radiotherapy (RT). In contrast, older patients who are deemed unfit for full-dose chemotherapy may receive reduced or partial chemotherapy regimens or RT alone. We describe the association between first-line treatment in older patients with HL and 3-year overall survival (OS). Methods We analyzed Surveillance, Epidemiology and End Results (SEER)-Medicare data from 1999-2014. Patients diagnosed with incident classical HL at age ≥65 years and enrolled in Medicare Part A and B fee for service were included. First-line treatment within 4 months of diagnosis was determined from inpatient, outpatient, and physician/supplier claims using chemotherapy J-codes, HCPCS codes, and DRG codes. Treatment was categorized as: 1) full chemotherapy regimen (e.g., ABVD/AVD), 2) partial chemotherapy regimen, 3) single chemotherapy drug or RT, or 4) no treatment. No treatment was defined by lack of claims for any treatment, which may result in misclassification. Three-year OS from time of diagnosis was estimated for all patients using the Kaplan-Meier method. Analyses comparing 3-year OS by treatment excluded the no treatment group because of immortal time bias (patients need to survive to treatment initiation) and lack of comparability with the treated groups even after adjustment (e.g., residual confounding by poor prognosis). Unadjusted 3-year OS was plotted by treatment category using the Kaplan-Meier method. A Cox proportional hazards model estimated hazard ratios (HR) and 95% confidence intervals (CIs) for the association between first-line treatment and 3-year OS, adjusted for age at diagnosis, race/ethnicity, Medicaid dual enrollment, comorbidity, frailty, diagnosis year, histology, stage, B symptoms, prior cancer, population density, and region. Adjusted HRs are also reported for patient and disease factors associated with 3-year OS. Results We included 2825 patients with a mean age of 76 years (SD=7). Patients received the following first-line treatments: 1197 (42.4%) full chemotherapy regimen, 503 (17.8%) partial chemotherapy regimen, 397 (14.1%) single chemotherapy or RT, and 728 (25.8%) no treatment. 92.3% of full chemotherapy regimens were ABVD/AVD. By 3 years post-diagnosis, OS for all patients was 46.7%. In unadjusted analysis including only treated patients (n=2097), those receiving full chemotherapy regimens experienced the highest 3-year OS, followed by single chemotherapy or RT, then partial chemotherapy regimens (Figure). In the Cox model adjusted for patient and disease factors, treatment with partial chemotherapy regimens (HR 2.12; 95% CI=1.75, 2.58) or single chemotherapy or RT regimens (HR 1.60; 95% CI=1.26, 2.03) were associated with a higher hazard of mortality by 3 years compared to treatment with full chemotherapy regimens. The adjusted Cox model also identified patient and disease factors associated with 3-year OS. Older patient age (HR 1.03 per year; 95% CI 1.01, 1.04), any comorbidity (HR 1.40; 95% CI 1.09, 1.79), frailty (HR 1.32; 95% CI 1.67), advanced stage (HR 1.45; 95% CI 1.22, 1.74), B symptoms (HR 1.59; 95% CI 1.31, 1.94), and lymphocyte depleted histology (HR 1.75 vs nodular sclerosis; 95% CI 1.17, 2.60) were associated with a higher hazard of mortality by 3 years. Conversely, lymphocyte rich histology (HR 0.57 vs nodular sclerosis; 95% CI 0.32, 1.00) had a lower hazard of mortality. Conclusions In a comprehensive analysis, we confirm poor outcomes of older patients with HL, with a 3-year overall mortality &amp;gt;50%. Although &amp;gt;40% of patients received full chemotherapy regimens, 25.8% had no documented treatment. Patients treated with full chemotherapy regimens had the highest 3-year OS compared to other treatment groups. Patients with no documented treatment may reflect a different subgroup of patients with poor prognosis, extensive comorbidity, or death before treatment initiation. Shared-decision making about treatment choices should consider competing risks of death from non-HL causes. Those who are able to tolerate full chemotherapy regimens, sequential therapy, or novel agents may benefit with significantly longer OS. Figure Disclosures Friedberg: Bayer: Honoraria, Other: Data &amp; Safety Monitoring Committee; Acerta: Other: Data &amp; Safety Monitoring Committee. Evens:Pharmacyclics: Honoraria, Other: DMC; Bayer: Consultancy, Honoraria; Research to Practice: Honoraria; Seattle Genetics: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; Affimed: Consultancy, Honoraria; Takeda: Research Funding; Merck: Research Funding.

Comparative Effectiveness of Lenalidomide, Bortezomib, and Their Combinations As First-Line Treatment of Older Patients with Myeloma

Background: In the S0777 phase 3 trial (Durie et al., Lancet. 2017), the lenalidomide, bortezomib, and dexamethasone (RVD) triplet showed survival advantage over lenalidomide/dexamethasone (RD) as initial therapy for myeloma. However, older transplant-ineligible patients often receive doublet regimens (RD or bortezomib/dexamethasone [VD]), or VD plus cyclophosphamide (VCD). In this setting, RVD has not been directly compared with doublets, or RD compared with VD, leaving an important gap in evidence. Our objective was to compare these regimens based on real-life data from older patients receiving first-line therapy for myeloma in the United States (US), using a causal inference approach. Methods: We identified Medicare beneficiaries with myeloma receiving first-line RD, VD, RVD, or VCD in 2007-2015, using Medicare claims linked to data from cancer registry (SEER-Medicare) covering ~35% of the US population, with successful linkage of &gt;95% individuals aged 65 or over. Patients had to have complete Medicare claims, including outpatient prescriptions (Part D), and we excluded cases with amyloidosis or end-stage renal disease. We used propensity score analysis to generate pseudo-randomized cohorts balancing multiple baseline factors, including socio-economic and performance status, time from diagnosis, presence of baseline hypercalcemia, renal disease, anemia, neuropathy, venous thromboembolism (VTE), and other comorbidities. In each comparative analysis, we fitted a separate propensity score, aiming at confounder balance measured by standardized difference of means &lt;0.10. After generating adequately balanced cohorts to minimize indication bias, we analyzed two survival endpoints (measured from start of first-line therapy): event-free survival (EFS, defined as start of a 2nd-line agent, hospice enrollment, or death, censored in case of an autologous transplant) and overall survival (OS), reporting hazard ratios (HR) with 95% confidence intervals (CI). We also compared select identifiable toxicities occurring within 6 months of starting therapy: hospitalization, anemia, neuropathy, and VTE, reporting relative risk (RR), as well as cumulative incidence function (CIF) for secondary solid tumors, reporting subhazard ratio (SHR). Results: We identified 6,076 eligible myeloma patients receiving first-line therapy between 2007 and 2015. Median age was 76 years [y], and there were 50% women. Between 2007 and 2015, the proportion of Medicare beneficiaries receiving RD increased from 18% to 25% (total N = 1,541; Fig. A), VD from 17% to 26% (N = 1,672), and RVD from 1% to 26% (N = 891). Median EFS in the study population was 0.88 y (95%CI, 0.83-0.93), and median OS was 2.7 y (95%CI, 2.6-2.8 y). Lenalidomide was dosed at 25mg in 58%. Bortezomib was dosed weekly in 57%. Detailed results of comparative models are shown in the Table. In the analysis of RVD versus (vs.) doublets, RVD showed better EFS (median 1.7 vs 0.8y; Fig. B) and OS (median 3.4 vs 2.7y). RVD resulted in higher rates of hospitalization (RR, 1.17; 95%CI 1.03-1.32), anemia (RR, 1.16; 95%CI 1.09-1.23), and neuropathy (RR, 1.49; 95%CI, 1.14-1.96), but no increased risk of VTE (RR, 1.06; 95%CI, 0.79-1.44). A higher proportion of patients treated with RVD underwent consolidative transplant (26% vs 6%). There was no significant difference in the risk of secondary cancers. Consistent findings were observed in the more specific comparison of RVD vs. RD (Table). In the analysis of RD vs. VD, RD demonstrated better EFS (median 1.0 vs 0.6y; Fig. C) and marginally better OS (median 2.7 vs 2.3y). RD resulted in more frequent VTE (RR, 1.44; 95%CI, 1.13-1.83), but less neuropathy (RR, 0.39; 95%CI, 0.29-0.53), without significant difference in hospitalization (RR, 0.96; 95%CI, 0.87-1.06) or anemia (RR, 0.95; 95%CI, 0.89-1.00). In the comparison of VCD vs. VD, there were no significant differences in EFS (Fig. D), OS, or observed toxicities. Conclusions: In this large, population-based study, first-line RVD shows EFS and OS advantage for older patients with myeloma who can tolerate higher potential short-term toxicity. RVD (or "RVD-lite" to minimize toxicity) should be the preferred regimen, but it is applied in only a minority of Medicare beneficiaries. For patients not eligible for the RVD triplet, an unexpected advantage of RD over VD was observed, suggesting that RD may be the preferred doublet. VCD appears to offer no benefit over the VD doublet. Disclosures Olszewski: Spectrum Pharmaceuticals: Research Funding; Genentech: Research Funding; TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding.

Comparative effectiveness of lenalidomide, bortezomib, and their combination as first-line treatment of older patients with myeloma

Phase 3 trials show the RVD (lenalidomide, bortezomib, and dexamethasone) triplet to be superior to RD (lenalidomide/dexamethasone) for initial therapy of myeloma. However, among older transplant-ineligible patients [pts], RVD has not been directly compared with doublets (RD or VD[bortezomib/dexamethasone]), nor has RD been compared with VD, leaving an important gap in evidence. We used population-based data to compare these regimens among older patients (Medicare beneficiaries) with receiving first-line therapy for myeloma.

Afatinib as First-line Treatment of Older Patients With EGFR Mutation-Positive Non-Small-Cell Lung Cancer: Subgroup Analyses of the LUX-Lung 3, LUX-Lung 6, and LUX-Lung 7 Trials

BackgroundAfatinib is approved in the US, Europe, and several other regions for first-line treatment for epidermal growth factor receptor mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC). Patients and MethodsTreatment-naive patients with advanced EGFRm+ NSCLC were randomized to afatinib (40 mg/d) versus cisplatin/pemetrexed (LUX-Lung 3 [LL3]) or cisplatin/gemcitabine (LUX-Lung 6 [LL6]), or versus gefitinib (250 mg/d; LUX-Lung 7 [LL7]). We report subgroup analyses according to age, including 65 years or older versus younger than 65 years (preplanned; LL3/LL6) and additional cutoffs up to 75 years and older (exploratory; LL7). Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated. ResultsAmong the 134 of 345 (39%) and 86 of 364 (24%) patients aged 65 years and older in LL3 and LL6, median PFS was improved with afatinib versus chemotherapy (LL3: hazard ratio [HR], 0.64 [95% confidence interval (CI), 0.39-1.03]; LL6: HR, 0.16 [95% CI, 0.07-0.39]). Afatinib significantly improved OS versus chemotherapy in elderly patients with Del19+ NSCLC in LL3 (HR, 0.39 [95% CI, 0.19-0.80]). Among the 40 of 319 patients (13%) aged 75 years or older in LL7, median PFS (HR, 0.69 [95% CI, 0.33-1.44]) favored afatinib, consistent with the overall population. Afatinib-associated AEs in older patients were consistent with the overall populations. ConclusionsSubgroup analyses of the LL3, LL6, and LL7 trials show that afatinib is an effective and tolerable treatment for patients with EGFRm+ NSCLC, independent of age.

New Firstline Treatment for Older Patients With Secondary AML

New Firstline Treatment for Older Patients With Secondary AML

Treatment of Hodgkin lymphoma in older patients

In this issue of Blood , [Forero-Torres et al][1][1][2] report encouraging results from a phase 2 study of brentuximab vedotin in the first-line treatment of older patients with Hodgkin lymphoma (HL). This is a population in whom frailty and comorbidity are common and outcomes poor when compared