The hedgehog pathway is implicated in resistance to anticancer therapies in glioblastoma (GB). GEINO1602 (NCT03466450) phase Ib/II study evaluated the safety and efficacy of glasdegib and the Stupp scheme in newly diagnosed GB. Patients received glasdegib with radiotherapy plus concomitant and 6 cycles of adjuvant temozolomide followed by glasdegib monotherapy. The recommended phase 2 dose was 75 mg/day of glasdegib. The primary endpoint was the 15-months overall survival (OS), with a futility threshold of 60% to consider the trial positive; accrual required 70 evaluable patients. 79 patients were enrolled. The 15 m OS rate was 52.1% (95% CI: 41.7-65.2). At 2 years, 29.2% of the patients were still alive. The median progression-free survival (PFS) was 7.1 months (95% CI: 6.2-8.6). Glasdegib plus chemoradiotherapy show preliminary efficacy. Despite not surpassing the futility threshold, 30% lived at the data cutoff. Translational research will help define the molecular traits of long-term survivors.

Maintenance avelumab has shown improved overall survival compared to chemotherapy alone in first-line treatment of advanced urothelial carcinoma. This study evaluates real-world evidence of avelumab as first-line maintenance therapy in patients with locally advanced or metastatic urothelial carcinoma (la/mUC). This was a multicenter, observational, retrospective and prospective study conducted in 22 Spanish centers. Patients were selected based on existing medical records of those treated with avelumab as first-line maintenance therapy before initiating the study (retrospective data), and those who continued to receive avelumab until the end of treatment or end of study (prospective data). Endpoints included median progression-free survival (mPFS), median overall survival (mOS) when available, PFS rate at 12 months (PFS12) and safety profile. Of the 125 patients enrolled, 113 were evaluable. The median follow-up of avelumab treatment was 10.7 months. Disease progression was the main reason for discontinuation in 70 (61.9

e16561 Background: The recommended treatment for patients with Stage IV Urothelial carcinoma is first-line platinum-based chemotherapy, followed by avelumab maintenance therapy in patients without disease progression. Real-world evidence (RWE) estimates the number of patients treated and the duration of treatments. Our objective was to assess the effectiveness and safety profiles of these patients in routine clinical practice. Methods: We conducted a multicentric, observational study with retrospective and prospective analysis of patients with stage IV Urothelial Carcinoma who started maintenance therapy with avelumab between January 2021 and April 2022 in 22 sites. Retrospective period included data from deceased patients and from alive patients prior to the signing of the informed consent (IC). Prospective period included patients’ data after signature of the IC. Results: Between September 2022 and July 2023, were enrolled 125 patients, 113 of whom were assessable for the analysis (74 alive and 39 deceased). The mean age was 69.6 years, 85.0% were male. Most of the patients had ECOG 1 (63.4%). Regarding the platinum treatment in first line, 54.0% of patients received cisplatin and 46.0% carboplatin, with a median of 4 cycles administered. Best response to avelumab in the retrospective evaluation was progressive disease (PD) in 25.5%, 43.3% stable disease (SD), 16.4% partial response (PR) and 12.4% complete response (CR). In the prospective period 16.7% reported PD, 54.2% SD, 12.5 PR and 14.6% CR. After a median follow up of 11,9 (8,3) months since the start of avelumab, 21 patients (18.6%) continued with avelumab, with a mean (SD) of 33.0 (12.1) cycles, and 81.4% of patients had stopped, with 12.9 (10.6) cycles administered. 67.3% of patients reported PD or exitus through the follow-up. The progression free survival probability (PFS) as primary endpoint was 0.2140, with a median (95% CI) PFS of 10.1 (7.1 – 12.4) months. The PFS probability at 12 months was 0.4492, with 52.2% of patients reporting PD or exitus. Moreover, 2.6% of patients (n=3) reported an exitus, all of them before 12 months, with an overall survival (OS) probability of 0.9542. The 5.3% of patients had SAEs -one resulted in death- most unrelated to avelumab. 39 patients (34.5%) had a total of 82 adverse drug reactions during the treatment period, 4 of them serious and 45.1% probably related to avelumab. The most frequent ADRs were asthenia and pruritus/rash; no SUSAR was reported. Conclusions: These data agree with the results of the phase 3 JAVELIN Bladder 100 trial and other real-world studies, confirming the effectiveness and manageable safety profile of avelumab 1LM in stage IV UC. Nonetheless, we acknowledge the limitations of our research, including its retrospective design. An extension study is being considered in order to have OS data for 24 months.

Abstract BACKGROUND IDH mutant gliomas are brain tumors with a high impact in quality of life and morbidity in the AYA (young adults and adolescents) population. It is a very heterogeneous disease with different treatment options and a new effective targeted therapy (vorasidenib) very well tolerated. More RWD is needed to advance faster in the best management of this population. METHODS A retrospective cohort study of all IDH mutant gliomas diagnosed from 2019 to 2023 in 21 Spanish centers, a total of 485 cases. This study includes data from a GEINO questionnaire (21 centers) and from the RETSINE (Spanish registry of CNS tumors). GEINO questionnaire includes 2021 WHO diagnosis, treatment strategy decision and how many remain in watch and wait (WW) strategy in 2024. RESULTS From 2019 to 2023, 485 cases of IDH mutant glioma were diagnosed in 21 centers, 67% astrocytomas (A) (326/485) and 33% oligodendrogliomas (O) (159/485). WW strategy was relatively frequent in low grade gliomas (LGG) 33% (75/226), and slightly more frequent in O grade 2 40% (41/103) than in A grade 2 28% (34/123). WW strategy was decided in only 3% of grade (gr) 3 IDH mutant gliomas (5/172). Despite this, with a very short follow-up, 24% (19/80) of WW population have ended up receiving treatment, radiotherapy (RT) or chemotherapy (CT). We have collected all data from 241 cases in RETSINE. Median age was 46 years old and 56% were male. Nearly half were glioma grade 2, 46% (67 A, 45 O), 32% grade 3 (49 A, 28 O) and 21% grade 4 (52). Complete resection was achieved in 35%, Karnofksy index (KPS) was superior to 80% in 70% and neurologic deficit at diagnosis was present in 35%. Almost 50% had epileptic seizures at diagnosis. Overall survival (OS) at 2 years is 94% (O gr2), 96% (O gr3), 91% (A gr2), 82% (A gr3) and 55% (A gr4) and progression-free survival at 2 years is 80% (O gr2), 91% (O gr3), 74% (A gr2), 51% (A gr3) and 27% (A gr4), with a median follow up of 1,8 years. Univariate analyses for OS in astrocytomas confirm the prognostic role of various factors: histologic grade 3-4 (HR 4.07; 1.56-10.6; p=0.004), KPS >80% (HR 0.19; 0.09-0.42; p<0.001); tumor size ≥ 6 cm (HR 2.53; 1.1-5.85; p=0.03) and previous neurologic deficit (HR 2.64; 1.27-5.49; p=0.01). WW population was enriched with complete resection and younger age (<40 years old). All detailed data of almost 600 patients or more will be presented at the congress, more centers will be included in this project. CONCLUSIONS RWD of IDH mutant gliomas in Spain demonstrates that WW is a strategy decision in 33% of LGG, 40% in oligodendrogliomas grade 2. Despite this, in short follow-up, 24% of these end up receiving RT and/or CT. RWD can help to better understanding the disease and optimize patient care strategies in the new era of IDH inhibitors. We should work on better quality data on registries, including quality of life parameters as capacity for work in this long-term disease with a high impact on morbidity.

90 Background: The Geriatric Assessment (GA) represents the future of the geriatric oncology to reduce toxicities and treatment-related hospitalization in the elderly. It has demonstrated results in predicting chemotherapy feasibility and response to docetaxel in patients with metastatic castration-resistant prostate cancer (MCRPca) (Della pepa). GA has also been explored in patients suitable to oral treatment (ref). In order to understand the prognostic capabilities of GA, we developed this analysis. Methods: All patients with MPCa sent to evaluation for Medical Oncology from January 2020 to August 2022 were analysed. GA was applied to those with 70 years or more. A geriatrician and/or an oncologist performed the evaluation. Informed consent was signed for patients. Ethical committee approved the protocol. Results: 85 patients were sent to Medical Oncology, 40 young (40%), 51 elderly (50%). Median age for young patients was 62 (46-68) and 79 for elderly (70-91). A comparison between populations is shown. This was an observational prospective study involving 51 patients who were 70 years of age or older. We performed GA including five domains and divided our patients into “fit”, “lower frailty,” and “high frailty” using Rockwood frailty scale. The relation between GC group and overall survival was explored. After GA, 26 were fit (51%), 16 had lower frailty (30%) and 10 had high frailty (19%). We found a statistically significant relationship between GA group and overall survival. Fit patients had overall survival of 27,1 months (22,8-31,5) versus 15,1 months (9,7-19,4) for low frailty and 5,6 months (3,2-7,9) for high frailty (p;0,000). Conclusions: Although our analysis has a selection bias as we only explored elderly patients sent to Medical Oncology, we found that a GA may help clinicians to recognize frail patients, and hence to reduce toxicities and early treatment discontinuation. We demonstrate its capability to be incorporated into routine clinical practice. [Table: see text]

Lung cancer (LC) is associated with ageing, with the average age of affected individuals being approximately 70 years. However, despite a higher incidence and prevalence among older people, the older adult population is underrepresented in clinical trials. For LC with Epidermal Growth Factor Receptor ( EGFR ) mutations, there is no clear association of this mutation with age. Geriatric assessments (GAs) and a multidisciplinary approach are essential for defining the optimal treatment. In this consensus, a group of experts selected from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (Sección de Oncogeriatría de la Sociedad Española de Oncología Médica—SEOM), the Spanish Lung Cancer Group (Grupo Español de Cáncer de Pulmón—GECP) and the Association for Research on Lung Cancer in Women (Asociación para la Investigación del Cáncer de Pulmón en Mujeres—ICAPEM) evaluate the scientific evidence currently available and propose a series of recommendations to optimize the management of older adult patients with advanced LC with EGFR mutations.

168 Background: Prostate cancer is the second most common cancer in men. A number of important systemic therapies have been developed to treat mCRPC and now comprise the current therapeutic landscape. Docetaxel became the first systemic therapy to improve survival in these men in a randomized study demonstrating superiority versus mitoxantrone (18.9 months versus 16.5, p=0,004). But, inexorably, after stopping, disease progresses. Methods: A prospective phase II trial was designed to test Olaparib maintenance efficacy, in terms of progression free survival (PFS), in patients with mCRPC with DNA-repair defects that have achieved partial or complete response after being treated with systemic therapy (at least six cycles of docetaxel). Results: 134 mCRPC patients were included since Feb-2018 to Nov-2020 and were tested for DDR alterations. 19.4% of patients had somatic mutations (30.8% BRCA2, 3.8% BRCA1, 19.2% ATM, 7.7% CHEK2, 7.7% PALB2). 53,8% received Olaparib maintenance treatment, with a median follow-up of 23.3 months. Median age was 73 years. Median basal PSA was 17 ng/dL. 100% were metastatic (14.3% de novo and 85.7% relapsed after primary treatment), 78.6% had bone metastasis, 35.7% visceral and 35.7% adenopathies. 42.9% had previous treatment with abiraterone and 35.7% with enzalutamide. 46.2% received at least 8 cycles of docetaxel. 7.1% achieved a partial response and 92.9% a disease stabilization. Response to Olaparib treatment was 14.3% partial response, 71.4% stabilization and 7.1% disease progression.14.3% had a PSA50 decrease. Median duration of response was 8.27 months. Median PFS was 10.1 months. Median PSA-PFS was 3.5 months. G3/4 adverse events were 21.4% asthenia,14.3% anemia and 7.1% neutropenia. Conclusions: Olaparib maintenance after at least six cycles of docetaxel shows promising activity in mCRPC with DDR alterations, with an acceptable toxicity profile. Our pathogenic mutations percentage (19,4%) is in line with previous publications. Clinical trial information: NCT03434158 .

e16524 Background: Survival of patients with metastatic renal cell carcinoma (mRCC) has improved with targeted therapies, but they are rarely curative and often result in therapeutic resistance. Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, known to influence tumor growth, metastasis, and angiogenesis. Aged fragile patients are not usually included in clinical trials and efficacy and tolerability of available treatments in this population are unknown. The aim of this trial is to evaluate safety and efficacy of cabozantinib in aged patients with mRCC. Methods: Pilot open-label, multicenter study that includes previously untreated fragile (G8 scale < 14 points and one or two reversible deficiencies in ADL-activities in daily life- or CISR-G grade 2 comorbidities or weight loss of 5-10% during the last 3 months) patients > 70 years old with histological or cytological diagnosis of mRCC, ECOG 0-2 and adequate organ function. Patients received cabozantinib 40 mg p.o. once daily until unacceptable toxicity or other reasons for treatment discontinuation. Dose can be escalated to 60 mg if 40 mg is considered tolerated and can be reduced to 20 mg if 40 mg is considered not tolerated. Results: Twenty patients are included in this interim analysis, 9 of them are still under treatment. Median age was 78 years, 70% were men and 68% had ECOG 0 and metastatic disease at diagnosis. None of them received radiotherapy. 55% of pts were vulnerable according to G8 score, 5% had grade 3 comorbidities according to CIRS-G scale, 20% had a score < 3 in mini-COG test, 100% had score < 10 in Gijon's social-familial evaluation scale, 25% were vulnerable according to Vulnerable Elders Survey 13 (score ≥3) and 45% were frail and at risk of disability according to Short Physical Performance Battery (score < 10). Median duration of treatment was 3.3 months (max. 20.4). In none of the patients was the dose escalated to 60 mg/d and in 7 patients was the dose reduced to 20 mg/d. Of the 12 patients evaluable for response, 2 achieved partial response and 7 stable disease, with a clinical benefit rate of 75%. Most frequent toxicities (all grades) were: asthenia (30%), diarrhea (25%), mucosal inflammation (15%), dysgeusia (15%) and hypothyroidism (15%). Reported grade 3 toxicities were thrombocytopenia, pyrexia and hypertension (5%). Two patients stopped study treatment due to toxicity: perforated ischemic colitis and skin toxicity. Conclusions: Safety profile in aged people is similar of that observed in previous studies. The frequency of toxicities is slightly lower than expected in this aged fragile population, probably because the patients received treatment at a dose of 40 mg/d, lower than the approved dose. Clinical trial information: NCT04134390.

Background: Inconsistent doses and schemes are commonly used in older patients receiving cancer chemotherapy. We performed this study in patients with cancer and age >_ 70 years to determine the frequency of undertreatment and overtreatment as well as factors influencing the decision to modify chemotherapy doses. Patients and Methods: Patients aged >_70 years starting new chemotherapy regimens were prospectively included in a multicentre study. The schedule and drug doses were determined by the treating oncologist. Pre chemotherapy assessment included sociodemographics, treatment details and geriatric assessment (GA) variables. Association between these factors and undertreatment (use of less intensive cancer treatment [LICT] in a fit patient) or overtreatment (use of standard cancer treatment in an unfit older patient) were examined by multivariate logistic regression. Results: Three-hundred ninety-seven patients were included, 43% of whom received LICT. If not adjusted for GA, toxicity did not differ between those receiving LICT (38%) or standard doses of chemotherapy (37%). If the dose of chemotherapy was analyzed according to the results of GA 61 (15%) patients had been undertreated and 133 (34%) had been overtreated. Undertreatment was related with increasing age and decreased renal function. Factors related with overtreatment were younger age, curative intention of treatment, prescription of G-CSF as primary prophylaxis and adequate cognitive status. Overtreated patients had more grade 3-4 toxicity than those receiving treatment adapted to fragility (42% vs 31%; p < 0.05). Conclusions: The use of chemotherapy without considering GA leads to overtreatment more commonly than undertreatment in older patients with cancer. Oncologists should take into account the results of GA to stratify patients and to avoid under or overtreatment. (c) 2020 Elsevier Ltd. All rights reserved.

Objective: To assess epidemiological, pathological and clinical characteristics, therapeutic management patterns and outcomes in the management of advanced ovarian cancer (AOC) in clinical practice. Methods: Multicenter, retrospective, epidemiological, observational real-world study reviewing clinical records from 277 patients diagnosed with AOC between January 2008 and December 2010 who were treated and followed in 31 Spanish hospitals belonging to the Spanish Ovarian Cancer Research Group (GEICO). Survival curves were estimated by Kaplan-Meier and differences analyzed by the log-rank test. Results: Median age at diagnosis was 62 years (range 26-96), 62% of patients had a high-grade serous carcinoma, and 64% and 21% of patients had stage IIIC and stage IV disease, respectively. Overall, 46% of patients underwent primary debulking surgery (PDS), with complete cytoreduction in 63% of procedures, and 34% underwent interval debulking surgery, with complete cytoreduction in 71% of them. Overall, 96% of patients received at least one cycle of front-line chemotherapy. Recurrence occurred in 77% of patients, and 90% of them (69% of total) received a second line chemotherapy. Median progression-free survival (PFS) was 14 months (95% CI: 13-17) and median overall survival (OS) was 41 months (95% CI: 34-49). PDS and complete cytoreduction had a statistically significant correlation with PFS and OS. Conclusions: This retrospective study provides real-world data of clinical characteristics, therapeutic management, and outcomes in Spanish AOC patients. Primary debulking surgery and complete cytoreduction were favorable prognostic factors in this series.

BACKGROUND Standard oncology tools are inadequate to distinguish which older patients are at higher risk of developing chemotherapy-related complications. MATERIALS AND METHODS Patients over 70 years of age starting new chemotherapy regimens were prospectively included in a multicenter study. A prechemotherapy assessment that included sociodemographics, tumor/treatment variables, and geriatric assessment variables was performed. Association between these factors and the development of grade 3-5 toxicity was examined by using logistic regression. RESULTS A total of 551 patients were accrued. Chemotherapy doses (odds ratio [OR] 1.834; 95% confidence interval [CI] 1.237-2.719) and creatinine clearance (OR 0.989; 95% CI 0.981-0.997) were the only factors independently associated with toxicity. Only 19% of patients who received reduced doses of chemotherapy and had a creatinine clearance ≥40 mL/minute had grade 3-4 toxicity, compared with 38% of those who received standard doses or had a creatinine clearance <40 mL/minute (p < .0001). However, no satisfactory multivariate model was obtained using different selection approaches. CONCLUSION Chemotherapy doses and renal function were identified as the major risk factors for developing severe toxicity in the older patient. These factors should be considered when planning to initiate a new chemotherapy regimen and should also lead to a closer follow-up in these patients. IMPLICATIONS FOR PRACTICE Older patients are more vulnerable to chemotherapy toxicity. However, standard tools are inadequate to identify who is at higher risk of developing chemotherapy-related complications. Chemotherapy doses (standard vs. reduced) and renal function were identified as the major risk factors for developing severe toxicity in the elderly. These factors should be considered when planning to initiate a new chemotherapy regimen and should also lead to a closer follow-up.

TPS5097 Background: Several studies have shown that long-term bladder preservation is feasible in selected patients with muscle-invasive bladder cancer, using a multimodal treatment, including transurethral resection (TUR), radiotherapy and chemotherapy. Durvalumab, a fully human monoclonal antibody against PD-L1, has shown activity in patients with advanced pretreated urothelial cancer. A preclinical study showed that the combination of radiation, anti-CTLA4 and anti-PD-L1 overcome- adaptive immune resistance and has superior activity than either therapy alone (Twyman-Saint Victor et al. Nature 2015). The purpose of the present study is to explore feasibility, toxicity and activity in terms of response and bladder preservation of the integration of TUR, immune double checkpoint inhibition with durvalumab and tremelimumab (a fully human monoclonal antibody against CTLA-4), and radiotherapy in the treatment of localized muscle-invasive. Methods: This is a multicenter prospective phase II study of multimodal therapy in patients with localized urothelial carcinoma of the bladder in clinical stages T2-4a N0 M0, ECOG 0- 1, without contraindications to immunotherapy, who either wish for bladder preservation or are ineligible for cystectomy. The primary endpoint is pathological response (≤T1) at post-treatment biopsy. A 2-stage sequential design (response rate P0=5, P1=0.7, α=0.10, β=0.20) requires at least 6 responses in the first 12 pts to expand to a second cohort of 20 patients. The treatment consists of initial TUR of the tumor, followed by durvalumab 1500 mg i.v. plus tremelimumab 75 mg i.v., every 4 weeks for 3 doses. Normofractionated external-beam radiotherapy is started 2 weeks later, at doses of 46 Gy to the minor pelvis and 64-66 Gy to the bladder. Patients with pathological response will be candidates to bladder preservation, whereas those with residual muscle invasive tumor will be candidates to salvage cystectomy. At present time, prespecified activity goal for the first stage of accrual was met; second stage accrual began in December 2019. Clinical trial information: NCT03702179 .

Background: Estimation of life expectancy in older patients is relevant to select the best treatment strategy. We aimed to develop and validate a score to predict early mortality in older patients with cancer. Patients and Methods: A total of 749 patients over 70 years starting new chemotherapy regimens were prospectively included. A prechemotherapy assessment that included sociodemographic variables, tumor/treatment variables, and geriatric assessment variables was performed. Association between these factors and early death was examined using multivariable logistic regression. Score points were assigned to each risk factor. External validation was performed on an independent cohort. Results: In the training cohort, the independent predictors of 6-month mortality were metastatic stage (OR 4.8, 95% CI [2.4–9.6]), ECOG-PS 2 (OR 2.3, 95% CI [1.1–5.2]), ADL≤5 (OR 1.7, 95% CI [1.1–3.5]), serum albumin levels ≤ 3.5 g/dL (OR 3.4, 95% CI [1.7–6.6]), BMI <23 kg/m2 (OR 2.5, 95% CI [1.3–4.9]), and hemoglobin levels < 11 g/dL (OR 2.4, 95% CI (1.2–4.7)). With these results, we built a prognostic score. The area under the ROC curve was 0.78 (95% CI, 0.73 to 0.84), and in the validation set, it was 0.73 (95% CI: 0.67–0.79). Conclusions: This simple and highly accurate tool can help physicians making decisions in elderly patients with cancer who are planned to initiate chemotherapy treatment.

Background. Standard treatment for glioblastoma is radiation with concomitant and adjuvant temozolomide for 6 cycles, although the optimal number of cycles of adjuvant temozolomide has long been a subject of debate. We performed a phase II randomized trial investigating whether extending adjuvant temozolomide for more than 6 cycles improved outcome. Methods. Glioblastoma patients treated at 20 Spanish hospitals who had not progressed after 6 cycles of adjuvant temozolomide were centrally randomized to stop (control arm) or continue (experimental arm) temozolomide up to a total of 12 cycles at the same doses they were receiving in cycle 6. Patients were stratified by MGMT methylation and measurable disease. The primary endpoint was differences in 6-month progression-free survival (PFS). Secondary endpoints were PFS, overall survival (OS), and safety (Clinicaltrials.gov NCT02209948). Results. From August 2014 to November 2018, 166 patients were screened, 7 of whom were ineligible. Seventynine patients were included in the stop arm and 80 in the experimental arm. All patients were included in the analyses of outcomes and of safety. There were no differences in 6-month PFS (control 55.7%; experimental 61.3%), PFS, or OS between arms. MGMT methylation and absence of measurable disease were independent factors of better outcome. Patients in the experimental arm had more lymphopenia (P < 0.001), thrombocytopenia (P < 0.001), and nausea and vomiting (P = 0.001). Conclusions. Continuing temozolomide after 6 adjuvant cycles is associated with greater toxicity but confers no additional benefit in 6-month PFS.

To evaluate the evolution of disease-related symptoms and its relationship with the control of the disease in first-line treatment in patients with metastatic non-small cell lung cancer (NSCLC).

11509 Background: Older patients have increased risk of toxicity from chemotherapy. The purpose of this study was to analyse predictive factors for developing grade 3-5 toxicity in older patients treated with chemotherapy. Methods: This prospective multicenter study included 500 cancer patients ≥ 70 years between Feb 2014 and Jun 2018. A prechemotherapy assessment including sociodemographics, tumor/treatment variables, laboratory test results, and geriatric assessment variables (function, comorbidity, cognition, psychological state, social activity/support, and nutritional status) was performed. Logistic regression was used to examine the association between these factors and the development of grade 3-5 toxicity. Results: Mean age of the patients was 77 years (70-92), ECOG PS 0/1/2: 25%/63%/12%. 223 (45%) had a primary dose reduction.167 (33%) patients developed grade 3-5 toxicity (28% grade 3, 5% grade 4, 1% grade 5). Univariate analysis found a higher risk of grade 3-5 toxicity in patients with creatinine clearance ≤ 60 mL/min, IADL ≤7, VES13 ≥ 6, and the administration of standard chemotherapy doses. In multivariable analysis, only the chemotherapy dose (odds ratio [OR] 1.179; 95% confidence interval [CI] 1.215–2.655) and creatinine clearance (odds ratio [OR] 0.989; 95% confidence interval [CI] 0.981–0.997) were independently associated with toxicity. Conclusions: Renal function and chemotherapy dose were significant predictors of grade 3-5 toxicity among older patients treated with chemotherapy.

Objective: The aim of this study was to assess a risk-adapted strategy for stage I seminoma guided by the presence of rete testis invasion. Methods: Between January 2013 and December 2015, a total of 135 consecutive patients with stage I seminoma from 18 Spanish tertiary hospitals were included in a prospective multicenter study. Median patient age was 38 years (range 22–60). Preoperative beta-human chorionic gonadotropin was elevated in 9.6% of patients. Rete testis invasion was present in 47.4% of patients. After orchiectomy, subjects with rete testis invasion were treated with 2 courses of adjuvant carboplatin (area under the curve of 7, with 21-day interval). Those without this risk factor were managed by surveillance. Disease-free survival (DFS) and overall survival (OS) were estimated with the Kaplan-Meier method. Results: After a median follow-up time of 33 months, only 6 relapses were recorded (5 on surveillance, 1 after carboplatin). These cases were rescued with BEP or EP chemotherapy, and all 135 patients are currently disease free without sequelae. Three-year DFS was 92.0 and 98.2% for patients on surveillance and after carboplatin, respectively. Three-year OS was 100%. Conclusion: A risk-adapted approach based on rete testis invasion as a single risk factor is feasible and yielded an excellent outcome with a 3-year DFS of 94.9%.

e22019 Background: Modification of initial chemotherapy (CT) doses and monotherapy treatment are common practices in elderly patient. However, age is not considered in clinical practice guidelines as a criterion for primary treatment modification (PTM). The aim of our study is to determine the frequency with which PTM is performed in elderly patients and to identify which factors are involved in making this decision. Methods: This is a multicentric, prospective study including patients 70 years or older who are initiating a CT treatment. Treatment schedule and dose were decided by the responsible physician. The prevalence of PTM was assessed as well as its association with treatment intent (curative vs. palliative), sociodemographic characteristics, laboratory data, geriatric assessment, tumor type and CT aggressiveness (MAX-2 score). Results: A total of 448 patients (mean age 77, range 70-92 years) were included. CT was administered with palliative intent in 294 patients and with curative intent in 154 patients. PTM was more common in the first group (59% vs. 42%; p < 0.001). Increasing age, MAX-2 score and the decision to prescribe G-CSF as primary prophylaxis were related to PTM in both groups. The Pfeiffer test was the variable independently associated with PTM in the group treated with palliative intent, whereas in the group treated with curative intent were plasma albumin levels and the IADL scale. Neither ECOG PS nor comorbidity were associated with PTM. There were no statistically significant differences either in grade 3-4 toxicity or in dose reductions in the PTM group. Conclusions: PTM is significantly more common in elderly patients treated with palliative intent. Factors associated with PTM include age, type of CT, Peiffer test, IADL scale and albumin.

Therapeutic decision-making for older patients with stage IV non-small-cell lung cancer (NSCLC) with no identifiable activating mutation is complex. In this prospective study, we evaluated the usefulness of geriatric assessment (GA) in identifying frail patients. Stage IV NSCLC patients ≥70 years of age were evaluated with GA and classified according to this evaluation into three different groups: fit, vulnerable and frail. Classifications based on GA, treatment decision, toxicity and overall survival were analysed. In total, 93 patients were included. Median age was 76 (70-92) years and 90% were men. Most patients had performance status (PS) 0 or 1 (82%), unrelated to their GA (p = 0.006). GA groups were associated with overall survival (p = 0.000), treatment decision (p = 0.0001), and toxicity (p = 0.0001). Chemotherapy was delivered to 100% of fit patients, to 48% of vulnerable patients, and to only 8% of frail patients (p = 0.000). Toxicity was higher in vulnerable patients than in fit individuals (p = 0.000). Multivariable analysis showed PS (p = 0.001), active treatment (p < 0.001) and GA group (p = 0.001) to be prognostic factors related to survival. Our results suggest that GA identified patients with poor natural prognosis.

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.