Pembrolizumab as first-line treatment for advanced NSCLC in older adults: A phase II clinical trial evaluating geriatric and quality-of-life outcomes.

OBJECTIVES: Since specific data on immunotherapy in older adults with advanced non-small cell lung cancer (aNSCLC) are scarce, we designed this study to determine the overall survival (OS) at one year of first-line pembrolizumab in patients older than 70 years with aNSCLC expressing PD-L1. Secondary objectives included progression-free survival, disease-specific survival, response rate, tolerability, quality of life (QoL) changes, and geriatric assessments. MATERIALS AND METHODS: A single-arm, open-label, phase II clinical trial was carried out by the Spanish Lung Cancer Group between February 2018 and November 2019 at ten active sites in Spain. We included patients 70 years old and older with histological or cytological documented stage IIIB or IV aNSCLC and PD-L1 expression ≥ 1%. Each subject received 200 mg of intravenous pembrolizumab every three weeks for a maximum of two years. RESULTS: 83 patients were recruited for the study and 74 were finally analysed. Most were male (N = 64, 86.5%) and former smokers (N = 51, 68.9%). 24 patients (32.4%) completed at least one year of treatment, 62 (83.7%) discontinued treatment, and 30 (40.5%) experienced disease progression. The median follow-up of our cohort was 18.0 months [range: 0.1-47.7] and 46 patients (62.2%) died during the period of study. The estimated OS at one year was 61.7% (95% CI: 49.6-71.8%) and the median OS of our cohort was 19.2 months (95% CI: 11.3-25.5). QoL tended to improve throughout the study, although the differences were not statistically significant. The main geriatric scores remained stable, except for a worsening in nutritional status (P = 0.004) and an improvement in frailty (P = 0.028). CONCLUSION: Our results support treating older adults with aNSCLC expressing PD-L1 with pembrolizumab in monotherapy. The stability of most geriatric scores and the positive trend on the patients' QoL should be highlighted, although our results did not reach statistical significance.

High Prevalence of Somatic Oncogenic Driver Alterations in Patients With NSCLC and Li-Fraumeni Syndrome.

INTRODUCTION: Actionable somatic molecular alterations are found in 15% to 20% of NSCLC in Europe. NSCLC is a tumor observed in patients with germline TP53 variants causing Li-Fraumeni syndrome (LFS), but its somatic molecular profile is unknown. METHODS: Retrospective study of clinical and molecular profiles of patients with NSCLC and germline TP53 variants. RESULTS: Among 22 patients with NSCLC and LFS (n = 23 lung tumors), 64% were women, median age was 51 years, 84% were nonsmokers, 73% had adenocarcinoma histological subtype, and 84% were diagnosed with advanced-stage disease. These patients harbored 16 distinct germline TP53 variants; the most common was p.R158H (5/22; three in the same family). Personal and family histories of cancer were reported in 71% and 90% of patients, respectively. In most cases (87%, 13/15), lung cancer was diagnosed with a late onset. Of the 21 tumors analyzed, somatic oncogenic driver mutations were found in 19 of 21 (90%), EGFR mutations in 18 (exon 19 deletion in 12 cases, L858R in three cases, and G719A, exon 20 insertion, and missing mutation subtype, each with one case), and ROS1 fusion in one case. A PI3KCA mutation was concurrently detected at diagnosis in three EGFR exon 19-deleted tumors (3/12). The median overall survival was 37.3 months in 14 patients treated with EGFR inhibitors; seven developed resistance, five (71%) acquired EGFR-T790M mutation, and one had SCLC transformation. CONCLUSIONS: Driver oncogenic alterations were observed in 90% of the LFS tumors, mainly EGFR mutations; one ROS1 fusion was also observed. The germline TP53 variants and lung cancer carcinogenesis driven by oncogenic processes need further evaluation.

Can we avoid the toxicity of chemotherapy in elderly cancer patients?

Although approximately 50% of cancer patients are 70 years of age or older, cancer treatment in the elderly remains a therapeutic challenge. The elderly form a very heterogeneous group in relation to their general health state, degree of dependence, comorbidities, performance status, physical reserve and geriatric situation, for which therapeutic decisions must be made in an individualized manner. In addition, changes in pharmacokinetics and pharmacodynamics of the drugs occur with age, as well as the tolerance of the tissues, leading to a narrowing of the therapeutic margin and an increase in toxicity. In the general population, Performace Status (PS) has traditionally been used to estimate tolerance to chemotherapy, but in the elderly population it is not useful. In this review we summarize the current knowledge about the pharmacology of antineoplastic drugs in the elderly and the tools available to help us identify risk of chemotherapy toxicity in these patients.

Geriatric assessment may help decision-making in elderly patients with inoperable, locally advanced non-small-cell lung cancer.

BACKGROUND: Although concurrent chemoradiotherapy (cCRT) increases survival in patients with inoperable, locally advanced non-small-cell lung cancer (NSCLC), there is no consensus on the treatment of elderly patients. The aim of this study was to determine the prognostic value of the comprehensive geriatric assessment (CGA) and its ability to predict toxicity in this setting. METHODS: We enrolled 85 consecutive elderly (⩾75 years) participants, who underwent CGA and the Vulnerable Elders Survey (VES-13). Those classified as fit and medium-fit by CGA were deemed candidates for cCRT (platinum-based chemotherapy concurrent with thoracic radiation therapy), while unfit patients received best supportive care. RESULTS: Fit (37%) and medium-fit (48%) patients had significantly longer median overall survival (mOS) (23.9 and 16.9 months, respectively) than unfit patients (15%) (9.3 months, log-rank P=0.01). In multivariate analysis, CGA groups and VES-13 were independent prognostic factors. Fit and medium-fit patients receiving cCRT (n=54) had mOS of 21.1 months (95% confidence interval: 16.2, 26.0). In those patients, higher VES-13 (⩾3) was associated with shorter mOS (16.33 vs 24.3 months, P=0.027) and higher risk of G3-4 toxicity (65 vs 32%, P=0.028). CONCLUSIONS: Comprehensive geriatric assessment and VES-13 showed independent prognostic value. Comprehensive geriatric assessment may help to identify elderly patients fit enough to be treated with cCRT.

Factors Predicting Adherence to a Tailored-Dose Adjuvant Treatment on the Basis of Geriatric Assessment in Elderly People With Colorectal Cancer: A Prospective Study.

BACKGROUND: Selecting elderly people with colorectal cancer (CRC) for adjuvant chemotherapy is challenging. Comprehensive geriatric assessment (CGA) can help by classifying them according to their frailty profile. The supposed benefit of chemotherapy is on the basis of the rate of treatment adherence. In this study we evaluated tolerance and adherence to tailored-dose adjuvant therapy on the basis of CGA in a cohort of older patients with high-risk stage II and stage III CRC. PATIENTS AND METHODS: This was a prospective study in 193 consecutive patients aged 75 years or older. On the basis of CGA results, we classified patients as fit, medium fit, or unfit, administering standard therapy, adjusted treatment, and best supportive care, respectively. We recorded planned chemotherapy, toxicity, and completion of the treatment. A logistic multivariate analysis was carried out. RESULTS: Seventeen (15%) of the 141 candidates for chemotherapy (n = 86 fit and n = 55 medium fit) refused treatment; associated factors included polypharmacy (odds ratio [OR], 5.34; 95% confidence interval [CI], 1.55-18.40) and rectal location (OR, 5.61; 94% CI, 1.45-21.49). Of the 105 (74%) patients receiving chemotherapy, 20 (27%) fit and 4 (13%) medium fit patients experienced Grade 3 to 4 toxicity (P = .11) without association to explanatory variables. Approximately 55% of patients treated with chemotherapy received at least 80% of the planned dose (55% fit and 58% medium fit patients; P = .7). Factors associated with completion of chemotherapy were the absence of toxicity (OR, 7.67; 95% CI, 2.41-24.43) and social support (OR, 2.29; 95% CI, 0.08-1.04). CONCLUSION: CGA is useful for selecting elderly patients for adjuvant chemotherapy, adapting the dose to their frailty profile, and identifying adherence-related factors amenable to modification through CGA-based interventions.

Delphi consensus of an expert committee in oncogeriatrics regarding comprehensive geriatric assessment in seniors with cancer in Spain.

OBJECTIVES: The aim of this work was to reach a national consensus in Spain regarding the Comprehensive Geriatric Assessment (CGA) domains in older oncological patients and the CGA scales to be used as a foundation for widespread use. MATERIAL AND METHODS: The Delphi method was implemented to attain consensus. Representatives of the panel were chosen from among the members of the Oncogeriatric Working Group of the Spanish Society of Medical Oncology (SEOM). Consensus was defined as ≥66.7% coincidence in responses and by the stability of said coincidence (changes ≤15% between rounds). The study was conducted between July and December 2016. RESULTS: Of the 17 people invited to participate, 16 agreed. The panel concluded by consensus that the following domains should be included in the CGA:(and the scales to evaluate them): functional (Barthel Index, Lawton-Brody scale, gait speed), cognitive (Pfeiffer questionnaire), nutritional (Mini Nutritional Assessment - MNA), psychological/mood (Yesavage scale), social-familial (Gijon scale), comorbidity (Charlson index), medications, and geriatric syndromes (urinary and/or fecal incontinence, low auditory and/or visual acuity, presence of falls, pressure sores, insomnia, and abuse). Also by consensus, the CGA should be administered to older patients with cancer for whom there is a subsequent therapeutic intent and who scored positive on a previous frailty-screening questionnaire. CONCLUSION: After 3 rounds, consensus was reached regarding CGA domains to be used in older patients with cancer, the scales to be administered for each of these domains, as well as the timeline to be followed during consultation.

Geriatric Assessment Predicts Survival and Competing Mortality in Elderly Patients with Early Colorectal Cancer: Can It Help in Adjuvant Therapy Decision-Making?

BACKGROUND: The challenge when selecting elderly patients with colorectal cancer (CRC) for adjuvant therapy is to estimate the likelihood that death from other causes will preclude cancer events from occurring. The aim of this paper is to evaluate whether comprehensive geriatric assessment (CGA) can predict survival and cancer-specific mortality in elderly CRC patients candidates for adjuvant therapy. MATERIAL AND METHODS: One hundred ninety-five consecutive patients aged ≥75 with high-risk stage II and stage III CRC were prospectively included from May 2008 to May 2015. All patients underwent CGA, which evaluated comorbidity, polypharmacy, functional status, geriatric syndromes, mood, cognition, and social support. According to CGA results, patients were classified into three groups-fit, medium-fit, and unfit-to receive standard therapy, adjusted treatment, and best supportive care, respectively. We recorded survival and cause of death and used the Fine-Gray regression model to analyze competing causes of death. RESULTS: Following CGA, 85 (43%) participants were classified as fit, 57 (29%) as medium-fit, and 53 (28%) as unfit. The univariate 5-year survival rates were 74%, 52%, and 27%. Sixty-one (31%) patients died due to cancer progression (53%), non-cancer-related cause (46%), and unknown reasons (1%); there were no toxicity-related deaths. Fit and medium-fit participants were more likely to die due to cancer progression, whereas patients classified as unfit were at significantly greater risk of non-cancer-related death. CONCLUSION: CGA showed efficacy in predicting survival and discriminating between causes of death in elderly patients with high-risk stage II and stage III resected CRC, with potential implications for shaping the decision-making process for adjuvant therapies. IMPLICATIONS FOR PRACTICE: Adjuvant therapy in elderly patients with colorectal cancer is controversial due to the high risk for competing events among these patients. In order to effectively select older patients for adjuvant therapy, we have to weigh the risk of cancer-related mortality and the potential survival benefits with treatment against the patient's life expectancy, irrespective of cancer. This prospective study focused on the prognostic value of geriatric assessment for survival using a competing-risk analysis approach, providing an important contribution on the treatment decision-making process and helping clinicians to identify elderly patients who might benefit from adjuvant chemotherapy among those who will not.

1ª Reunión Nacional de Trabajo Multidisciplinar en Oncogeriatría: documento de consenso / 1st National Meeting of Multidisciplinary Work in Oncogeriatrics: Expert Consensus Document

El pasado día 2 de junio de 2011 el Institut Català d’Oncologia l’Hospitalet-Hospital Duran i Reynals acogió la primera Reunión de Trabajo Multidisciplinar en Oncogeriatría. La idea de la reunión, iniciativa de las Sociedades Médicas de Oncología Radioterápica, Geriatría y Gerontología, Cuidados Paliativos y Oncología Médica, fue la de iniciar una línea de trabajo conjunta entre las diferentes especialidades que intervienen habitualmente en el manejo del paciente de edad avanzada con patología oncológica. En este documento se recoge un resumen de los temas tratados(AU)

On 2nd of June 2011 the Institut Català d’ Oncologia l’Hospitalet--Hospital Duran i Reynals hosted the first Meeting of Multidisciplinary Work in Oncogeriatrics. The reason for the meeting, which follows on from an initiative of the Medical Societies of Radiotherapy, Oncology, Geriatrics and Gerontology and Palliative Care and Medical Oncology, was to initiate a joint line of work among the different specialties that generally take part in the handling of the elderly patient suffering from oncologic pathologies. This document summarises the different subjects covered during the Meeting(AU)

[1st National Meeting of Multidisciplinary Work in Oncogeriatrics: expert consensus document]. / 1.(a) Reunión Nacional de Trabajo Multidisciplinar en Oncogeriatría: documento de consenso.

On 2nd of June 2011 the Institut Català d' Oncologia l'Hospitalet--Hospital Duran i Reynals hosted the first Meeting of Multidisciplinary Work in Oncogeriatrics. The reason for the meeting, which follows on from an initiative of the Medical Societies of Radiotherapy, Oncology, Geriatrics and Gerontology and Palliative Care and Medical Oncology, was to initiate a joint line of work among the different specialties that generally take part in the handling of the elderly patient suffering from oncologic pathologies. This document summarises the different subjects covered during the Meeting.