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8501 Background: Non-small cell lung cancer (NSCLC) is incurable in most patients with locally advanced stage IIIA disease. Previous results indicate that the use of neoadjuvant chemoimmunotherapy could increase the percentage of cured patients being a promising therapeutic option that has to be tested in randomized clinical trials. Methods: NADIM II (NCT03838159) is an open-label, randomized, two-arm, phase II, multi-center clinical trial. Patients with resectable clinical stage IIIA (per AJCC 7th ed) NSCLC, ECOG PS 0-1, and no known EGFR/ALK alterations were randomized to receive Nivolumab (NIVO) 360mg + Paclitaxel 200mg/m2 + Carboplatin AUC5 for 3 cycles every 21 days (+/- 3 days) as neoadjuvant treatment followed by surgery, or Paclitaxel 200mg/m2 + Carboplatin AUC5 for 3 cycles every 21 days (+/- 3 days) followed by surgery. Patients with R0 resection confirmed by pathological evaluation initiated adjuvant administration of NIVO within the 3rd to 8th week (+7 days) from surgery and for 6 months. The primary endpoint was pathological complete response (pCR) by blinded independent pathological review (BIPR) in the intent-to-treat population (ITT). pCR was defined as 0% viable tumor cells in resected lung and lymph nodes; patients who did not undergo surgery were classified as non-responders. Major pathological response (MPR; ≤ 10% viable tumor) per BIPR, overall response rate (ORR), toxicity profile, and potential predictive biomarkers are secondary endpoints. Results: Between February 8, 2019, and November 11, 2021, 90 patients were enrolled, of whom 87 patients were valid. Neoadjuvant NIVO + chemo significantly increased the pCR rate compared to chemo in the ITT (36.2% vs 6.8%; Relative Risk (RR) 5.25 [99% CI 1.32-20.87]; P = 0.0071). NIVO + chemo also improved MPR rates vs chemo in the ITT (52 % vs 14 %), as well as ORR (74 % vs 48%). Definitive surgery occurred for 91% of pts treated with NIVO + chemo and 69% with chemo; surgery was cancelled rarely due to AEs (1 pts/experimental arm) and due to disease progression in 1 and 4 pts in the experimental and control arm respectively. Grade 3-4-related AEs were reported in 24 % vs 10% in the NIVO + chemo vs chemo arms, respectively. In the ITT experimental arm, patients with pCR had higher PD-L1 TPS (median 70%, IQR 5-90%) compared to non-responders (median 0%, IQR 0-37.5%, P = 0.0035). AUC to predict pCR was 0.734 (95% CI 0.59-0.88; P = 0.005). The pCR rate rises across increasing categories of PD-L1 TPS ( < 1% 14.3%; 1-49% 41.7%; ≥50% 61.1%; P = 0.008). Conclusions: This study confirms the superiority of the chemo-immuno combination in patients with resectable stage IIIA NSCLC in terms of pCR, as well as the feasibility of surgery, with a moderate increase in grade 3-4 toxicity. Thus, this treatment should become the standard of care in these patients. Clinical trial information: NCT03838159.

To investigate the efficacy of alternating cycles of sunitinib and everolimus vs standard sequential treatment of sunitinib followed by everolimus in first-line metastatic renal cell carcinoma (mRCC), as alternating blockade of vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin (mTOR) pathways could potentially prevent the occurrence of resistance to anti-VEGFR therapy in mRCC.SUNRISES, a randomised open-label Phase II study, investigated the efficacy of alternating cycles of sunitinib and everolimus vs standard sequential treatment of sunitinib followed by everolimus upon progression. Treatment-naïve patients with clear-cell mRCC were included. Alternating treatment consisted on 12 weeks of sunitinib, followed by 12 weeks of everolimus. The primary endpoint was the progression-free survival (PFS) rate at 1 year. The secondary endpoints included the median PFS, overall survival (OS), response rate, and safety.Accrual was low due to the advent of new-generation therapies, and the study was stopped prematurely. Only 41 patients out of the planned 102 patients were accrued, and randomised in a 2:1 ratio (15 patients to the control arm, 26 to the experimental arm). In all, 60.9% of patients had performance status (PS) 0 and 39% PS 1; 63% had a favourable prognostic risk profile, while 36% were intermediate risk. The primary endpoint was not met. The 1-year PFS rate was 49.7% (experimental arm) vs 84.62% (control arm; P = 0.11). There was a trend towards fewer Grade ≥3 adverse events with the alternating approach (50% vs 73.3%; P = 0.14). The median OS was similar in both treatment arms. The other secondary endpoints favoured the control arm.The study failed to show any benefit of alternating cycles of sunitinib and everolimus in patients with mRCC. The alternating approach using an mTOR inhibitor does not seem to prevent the occurrence of resistance to VEGFR blockade.

Background Malignant mesothelioma is a rare but aggressive tumor arising from the pleura, typically associated with exposure to asbestos. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns, and outcomes in Spain. Material and methods Patients diagnosed with malignant mesothelioma of the pleura were recorded in an anonymous online database (BEMME, Epidemiologic Spanish Malignant Mesothelioma Database) from June 2008 through May 2013. Patient and tumor characteristics at time of diagnosis, as well as subsequent treatments (surgery, radiation, and chemotherapy), were collected. Among patients treated with chemotherapy, we explored type of chemotherapy regimen and outcomes by treatments. Results A total of 560 malignant pleural mesothelioma (MPM) patients were recorded. The median age at diagnosis was 68 years, mainly with epithelioid histology (62 %), and any asbestos exposure was noted in 45 % of patients. Nearly two-thirds of patients (71 %) received chemotherapy, mainly platinum-pemetrexed combination, as part of their treatment. Surgery and radiotherapy were given in 36 % and 17 % of patients, respectively. The median overall survival (OS) in the whole cohort was 13.0 months (95 % confidence interval (CI), 11.1–14.8 months) with 1-year OS of 53.2 % (95 % CI, 48.7–57.7 %). In patients receiving first-line chemotherapy (N = 315), the median OS was 13.4 months (95 % CI, 10.8–16.0 months), reaching 20.2 months (95 % CI, 17.2–23.2 months) for those 68 patients receiving maintenance chemotherapy. Results of multivariate analyses showed significant association of ECOG-performance status, histology and treatment response with improved OS in MPM patients treated with palliative chemotherapy. Conclusions Despite multimodal therapeutic intervention, survival of patients with mesothelioma in Spain remains poor. Although it did not reach significance in the multivariate analysis, a meaningful additional survival benefit was observed among those patients receiving maintenance chemotherapy.

e18674 Background: In 2019, we used the American Society of Clinical Oncology (ASCO) Quality Training Program (QTP) as an instrument to improve the inclusion rate in clinical trials (CTs) for bladder cancer patients from 24% in 2018 to 43,75% in 2019. CTs play an important role in developing new treatments, expanding or refining treatments that are already available, and/or identifying behavioral changes that can prolong or improve the lives of subjects. Therefore, we believe it is important for patients and for society to maintain the inclusion rate in clinical trials despite COVID-19 pandemic. Methods: We collected the number of bladder cancer patients evaluated for the first time in the Oncology department, the number of patients who were offered a clinical trial, the screen failures and the number of patients enrolled in CTs. Results: In 2019, we were able to increase the enrollment rate in CTs for bladder cancer patients to from 24% to 43,75% thanks to the ASCO-QTP. With this program we created a list of measures and identified the ones that would have a greater impact. The one that seems to have had the highest impact is the diffusion of CTs in the Investigation Unit and the Genitourinary (GU) board. In 2020, thanks to this measure and despite the COVID-19 pandemic, we were able to maintain a 40,81% enrollment rate. When analyzing the patients evaluated for the first time in the Oncology department, 48 in 2019 and 49 in 2020, there were some interesting differences. In 2020, 42,86% had stage IV disease with respect to 39,6% in 2019, and only 22,44% had non-muscle invasive disease (NMIBC) versus 33,33% in 2019. However, thanks to the diffusion of CTs in the Investigation Unit and in the GU-board, which translates in an early derivation of patients to Medical Oncology and an increase in the number of available CTs, we were able to offer a CT to 73,5% of patients in 2020 against 60,4% in 2019. Although there was an increase of screen failures in 2020 (32,65% vs. 16,66%), 50% of them were due to the absence of a biomarker in a biomarker driven CT, with respect to 25% in 2019. Conclusions: Using ASCO-QTP as an instrument, we identified the importance of the diffusion of CTs and the close collaboration between departments. Maintaining these measures, we were able to uphold the inclusion rate in CTs for bladder cancer patients in 40,81% despite the later diagnosis of patients due to COVID-19 pandemic.

TPS8581 Background: The results of current studies are considered acceptable evidence to support the hypothesis of efficacy of the proposed combination of immunotherapy with chemotherapy (CT-IO) in patients with NSCLC stages Ib-IIIA candidates for adjuvant treatment. Methods: This is an open-label, randomised, two-arm, phase III, multi-centre clinical trial. Primary objective and endpoint: The primary objective is disease free survival (DFS) defined time from randomization to the earliest event defined as disease recurrence, any new lung cancer (even in the opposite lung), or death from any cause at any known point in time Sample size: 210 patients NSCLC stages Ib-IIIA (Experimental Arm (Adjuvant Chemotherapy-Inmunotherapy + maintenance adjuvant Inmunotherapy): 105 patients, Control Arm (Adjuvant Chemotherapy): 105 patients Treatment Patients randomised to the experimental arm will receive Nivolumab 360mg + Paclitaxel 200mg/m2 + Carboplatin AUC5 for 4 cycles every 21 days (+/- 3 days) as adjuvant treatment followed by maintenance adjuvant treatment for 6 cycles with Nivolumab 480 mg Q4W (+/- 3 days). Patients randomized to the control arm will receive Paclitaxel 200mg/m2 + Carboplatin AUC5 for 4 cycles every 21 days (+/- 3 days) followed by 2 observation visits. Total trial duration: 6.5 years, 3.5 years of recruitment, 1 year of adjuvant treatment or observation and 2 years of follow up. The start date was January 2021. The estimated primary completion date is June 2027. Clinical trial information: NCT04564157.

[Background/Aim] First-line bevacizumab-based therapies have been shown to improve clinical outcomes in patients with non-squamous non-small-cell lung cancer (NSCLC). We aimed to descriptively analyse patients with non-squamous NSCLC who received a long-term period of maintenance bevacizumab., [Patients and methods] This retrospective study included 104 patients who had already reached a progression-free survival (PFS) of at least 9 months., [Results] Median overall survival and PFS were 30.7 and 15.1 months, respectively. The overall response rate was 83 %. Weight loss ≤5 %, ECOG PS = 0, or low number of metastatic sites seem to be predictive factors of good evolution. The incidence of bevacizumab-related adverse events appeared to be similar as the previous studies., [Conclusion] Our findings show that there is a long-term survivor group whom the administration of bevacizumab resulted in a relevant prolongation of response without new safety signals. Due to the population heterogeneity, it was not possible to identify the standardised predictive factors., This work was supported by Roche Farma, S.A., Spain.

Background CT-RT is the standard treatment for unresectable LA-NSCLC. P plus vinorelbine is widely used. Metronomic CT is a frequent administration of low doses of CT. mOV has shown good efficacy and improved safety, and could improve the RT effect. Our goal is to evaluate the efficacy and safety of P-mOV with radical RT in patients (pts) with LA-NSCLC. Methods Pts aged 18-75 years with histologically proven untreated and unresectable LA-NSCLC, adequate bone marrow, hepatic & renal function, ECOG PS0-1, received P 80mg/m2 D1 every 3 weeks combined with mOV 50mg/day on days D1, 3 & 5/weekly, 2 cycles (cy) as induction; patients without progression received 2 more cy of P at the same dose with mOV 30mg/day on D1, 3 & 5/weekly, concurrently with RT (66Gy in 6.5weeks). Primary endpoint was progression-free survival (PFS) by RECIST v1.1; secondary endpoints were: overall response rate (ORR), disease control rate (DCR), overall survival and safety profile. To guarantee an overall type-1 α error no greater than 0.05 and a type II (β) error 0.1 for PFS, a sample size of 67 pts was planned. Results Sixty-seven pts were recruited in 17 Spanish sites from 04/2016 to 06/2017. One of them didn’t meet all the inclusion criteria. We analyzed 66 pts included. Pt characteristics: Male 77.3%; median age 62 (range 33-75); PS 0/1 52/49%; smokers 53%; adenocarcinoma/squamous 43.9/42.4%; stage IIIA/B 42.4/57.6%. Only 32.3% of pts presented any grade 3-4 adverse event, including: neutropenia 20.0%; anemia 4.6%; febrile neutropenia 6.2%; esophagitis 3.1%; pneumonitis 1.5%. There were two deaths non-related to the treatment, during this period. Fifty-one pts have completed the treatment. ORR: 67.7%. DCR: 84.6%. With a median follow-up of 22.3 months (range 1.1-34.9), the median PFS is 11.5 months (CI95%; 9.9-15,4). Conclusions mOV-P with RT is as effective as the standard administration of vinorelbine, improving its safety profile. Clinical trial identification EudraCT 2015-003312-21. Legal entity responsible for the study Spanish Lung Cancer Group. Funding Pierre Fabre. Disclosure All authors have declared no conflicts of interest.

Background Post-operative platinum-based chemotherapy is the standard of care for resected NSCLC with nodal involvement. Expression of genes involved in DNA repair may have a prognostic role for the outcome. BRCA1 plays an important role in DNA repair pathways and could have a prognostic impact in this setting. The SCAT trial results found that for low BRCA1 levels subgroup Cis-Gem was superior to Cis-Doc and in high BRCA1 subgroup docetaxel single agent without platinum achieved similar survival to Cis-Doc. Risk of recurrence analysis according BRCA-1 levels has been performed. Methods From Jun/2007 to May/2013 591 patients were screened and 500 were included, 108 in the control arm treated with Cis-Docetaxel and 392 in the experimental arms treated with Cis-Gem, Cis-Doc or docetaxel alone according to terciles of BRCA1 expression level. With a cut-off September 30th 2018 and a median follow-up of 60 months, recurrence patterns were analysed for the whole group according BRCA1 levels in tumor tissue and comparison were made for risk of recurrence, single/multiple recurrence, thoracic/extrathoracic and metastatic sites (liver, bone, brain). Results Cumulative recurrence was evaluable in 232/456 patients (50.8%), 182/354 patients treated in the experimental arm and in 50/102 patients treated in the control arm (RR 1.04; 0.83-1.30) (p = 0.672). The majority of recurrences 159/232 (68.5%) were single site intrathoracic recurrences in 121/232 (52%) while 111/232 were extrathoracic (47.8%). Overall recurrence was 56.5% (113/200 p) for low tercile BRCA1 vs 48.8% (63/129) for intermediate tercile vs 44% (56/127) for high tercile (p = 0.025). No differences were seen between tercile groups for single site (p = 0.35), multiple site (p = 0.26), intrathoracic (p = 0.36), or extrathoracic (p = 0.38). More frequent distant metastatic sites were: bone (42 patients), brain (38 patients) and liver (11 patients). RIsk reduction was seen for brain metastases in patients with higher tercile BRCA1 (p = 0.003). Conclusions For NSCLC resected patients with lymph node involvement risk of recurrence remains high with a cumulative rate > 50%. Relative risk of recurrence was lower for tumors with higher BRCA1 levels. Distant metastases were seen in 47.8% of patients. Brain metastases risk was significant lower for patients with low BRCA1 expression. BRCA1 levels acts as a prognostic factor in early stages NSCLC. Clinical trial identification EudraCT: 2007-000067-15; NCT 00478699. Legal entity responsible for the study Spanish Lung Cancer Group - Grupo Espanol Cancer de Pulmon. Funding Sanofi Aventis. Disclosure All authors have declared no conflicts of interest.

Background Target therapy guide by biomarkers have become the standard of care for patients with lung cancer (LC). So, identify those molecular alterations is one of the most important care needs nowdays. Our objective was to know the implementation degree of these tests in a large cohort of patients in Spain using the Thoracic Tumor Registry (TTR) of the Grupo Espanol de Cancer de Pulmon (Spanish Lung Cancer Group). Methods The TTR is an observational cohort multicenter study of LC in Spain. The study is conducted according to the Declaration of Helsinki and approved by the institutional review board of each participating institute. The registry was approved by the Spanish Drug Agency as a non-post-authorization, non-interventional study. We analyzed the molecular biomarkers considering all stages of LC. Results A total of 7,872 patients from 58 Spanish centers were enrolled between August 2016 to December 2018. The most frequent screened molecular test was the EGFR mutations, it was performed in 4,456 patients (67.5%). The proportion of biomarker evaluation has varied over time, ranging from 57.9% prior to 2012 up to 73.7% in 2017. The molecular assessment of some biomarkers reached 81.4% of these patients, with some differences between Regional Communities, regarding the molecular tests performed. Three thousand four hundred forty-six (3,446) patients (52.2%) had a stage IV at diagnosis. There was performed some biomarker test in 92% of the 2570 patients with stage IV and non-squamous histology. In those stage IV non-squamous patients, the EGFR and ALK test were performed in 92% and 79% respectively but 2 years ago ALK test was done only in 40% of the patients. ROS1 was studied in 20% of the cases. Conclusions Although no national plan exists for molecular biomarker analysis in Spain, the implementation of biomarkers tests in all the hospitals that contribute to the TTR is high. The increase in the ALK analysis in the last period is relevant. As we have some regional differences, it is important to understand the causes to improve them. Clinical trial identification NCT02941458. Legal entity responsible for the study Spanish Lung Cancer Group. Funding Novartis, Merck Sharp and Dohme, Lilly. Disclosure All authors have declared no conflicts of interest.

Background Tobacco use, mainly as cigarette smoking, is the leading cause of lung cancer. Eighty-five percent of LC occur in smokers. Understanding the Spanish smoking habits allows the government to design health care policies against this consumption. To do so, the Grupo Espanol de Cancer de Pulmon (Spanish Lung Cancer Group) made this analysis within the context of the Thoracic Tumor Registry (TTR). Methods The TTR is an observational cohort multicenter study in Spain. The study is conducted according to the Declaration of Helsinki and approved by the institutional review board of each participating site. The registry was approved by the Spanish Drug Agency, as a non-post-authorization, non-interventional study. Results Data have been collected from 6,600 LC from 58 different hospital sites across Spain. 12% (866 p) were non-smokers, 46% (3,039 p) were former smokers and 39% (2,611 p) were smokers. There were significant differences by gender, more women were non-smokers (37 % vs. 45% in males), meanwhile more former smokers were male (53.4% vs. 27.9% in women) (p-valor Conclusions Tobacco use is the leading cause of LC in Spain accounting 85% of the cases. Consumption has increased in both genders, but specially in women, in our country among lung cancer patients. Tobacco cessation campaigns, especially in women, should be a priority in western countries, like Spain, and it has to be adapted to regional differences in tobacco use. Clinical trial identification NCT02941458. Legal entity responsible for the study Spanish Lung Cancer Group. Funding Novartis, MSD, Lilly. Disclosure M. Provencio: Advisory / Consultancy: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim. All other authors have declared no conflicts of interest.

e14083 Background: Several checkpoint inhibitors antibodies have been approved to treat bladder cancer, and many trials are still ongoing. However, few data about their efficacy and safety outside of a clinical trial have been published. Here we report our experience in managing immune-related toxicity in our daily practice. Methods: We performed a retrospective analysis of 23 patients (pts) with metastatic bladder cancer treated with checkpoint inhibitors in Clínico San Carlos University Hospital from April 2016 to September 2018. The aim of this study is to evaluate the safety of checkpoint inhibitors in daily practice. Results: Median age was 75 years (range 53-92) and 75% were men. The performance status at the beginning of immunotherapy treatment was 0 in 4 pts (17.4%), 1 in 16 pts (69.6%) and 2 in 3 pts (13%). Thirteen pts (56.5%) received the treatment as first line, 6 (26.1%) as second line and 4 (17.4%) as third line and beyond. 18 pts (78.3%) received immunotherapy as monotherapy (15 pts Atezolizumab and 2 pts Pembrolizumab), 3 pts (13%) received an immunotherapy combination with Durvalumab plus Tremelimumab, and 2 pts (8.7%) received chemotherapy plus immunotherapy (Carboplatin plus Avelumab or Atezolizumab). Of the analyzed patients, 36% did not develop any immune related adverse event (irAE). However, 64% did present some side effect. The most common side effect was asthenia (12.5%), cutaneous (8.3%), endocrine (5.6%), gastrointestinal (4.2%) and hepatic (2.8%). Only16.6% of the events required some kind of treatment (9.7% required steroids). Three patients had grade 3 or 4 toxicity, 1 patient on Atezolizumab presented with grade 3 diarrhea and grade 3 hepatic toxicity, another patient on Atezolizumab presented two heart attacks after the two infusions and eventually died, lastly a patient on Durvalumab + Tremelimuab suffered grade 3 hypophysitis. Conclusions: Incidence and therapeutic management of irAEs occurring in our clinical setting closely resembles that reported in retrospective series even though they were mostly elderly patients and many of them were heavily pretreated. Increasing our experience and knowledge in the clinical setting will improve and optimize the use of these drugs.

Background/Aim: Erlotinib and chemotherapy have shown similar efficacy for pretreated non-small cell lung cancer (NSCLC) patients, but none of the large studies have selected patients based on histology. We present a retrospective single-center series of advanced non-squamous NSCLC patients treated with erlotinib or pemetrexed as second-line therapy. Our aim was to compare the efficacy and safety data under clinical practice conditions and to identify subgroups of patients who could benefit more from these therapies. Methods: A total of 88 patients were included. Squamous histology was our main exclusion criterion. EGFR mutation status was known for 54.5% of the patients; 6 patients treated with erlotinib and 2 with pemetrexed had EGFR-mutated tumors. Smoking history was analyzed as possible predictive factor of efficacy. Results: No significant differences in progression-free survival (PFS; 3 vs. 2.5 months, p = 0.06) or overall survival (OS; 4.9 vs. 7.4 months, p = 0.733) between the erlotinib and pemetrexed groups were found in the overall population. EGFR wild-type patients had a similar median PFS with erlotinib compared to pemetrexed (2.7 vs. 2.3 months, p = 0.42), with no statistical differences in OS. Statistically significant differences in OS in favor of pemetrexed for current smokers (3 vs. 7.1 months, p = 0.017) were found, while erlotinib achieved significantly better PFS in never-smokers compared to former smokers (3.5 vs. 2.7 months, p = 0.005). Serious adverse events were uncommon but more frequent with pemetrexed, and were mainly related to hematologic toxicity. Conclusions: Erlotinib should be considered as another equal option in second-line treatment for EGFR wild-type patients as well as for subpopulations with unknown mutational status. Smoking history could be a useful clinical marker to choose a second-line treatment.

9047Background: Atezo (anti–PD-L1) + bev (anti-VEGF) + chemo prolonged PFS vs bev + chemo in patients (pts) with 1L nonsquamous mNSCLC in the randomized, Phase III IMpower150 study. PRO data, inclu...

e13608Background: The Spanish Lung Cancer Group (GECP) initiated a Tumor Thoracic Register (RTT) in September 2016 with the aim of evaluating accurate, basic data concerning this oncological pathol...

Chemotherapy-induced neutropenia, the major dose-limiting toxicity of chemotherapy, is directly associated with concomitant morbidity, mortality and health-care costs. The use of prophylactic granulocyte colony-stimulating factors may reduce the incidence and duration of chemotherapy-induced neutropenia, and is recommended in high-risk patients. The objective of this study was to develop a model to predict first-cycle chemotherapy-induced neutropenia (defined as neutropenia grade>or=3, with or without body temperature>or=38 degrees C) in patients with solid tumours. A total of 1194 patients [56% women; mean age 58+/-12 years; 94% Eastern Cooperative Oncology Group (ECOG) status

Background: The purpose of this study is to evaluate the impact on the health-related quality of life (HRQoL) of sunitinib versus interferon-alpha (IFN-α) treatment in patients with metastatic renal cell carcinoma (mRCC). Patients and methods: In all, 304 mRCC patients (European cohort) were randomized 1 : 1 to receive sunitinib (50 mg/day for 4 weeks, followed by 2 weeks off) or IFN-α (9 million units s.c. injection three times/week). The following questionnaires were completed (days 1 and 28 per cycle): Functional Assessment of Cancer Therapy-General (FACT-G), the FACT-Kidney Symptom Index and the EuroQol Group's EQ-5D self-report questionnaire (EQ-5D). Results correspond to an ongoing trial with progression-free survival time as primary end point, and patients were still being followed up. Data were analyzed using repeated measures mixed effects models (MEMs) that allow the inclusion of initial differences and uncompleted repeated measures, with the assumption of data missing at random. Six-cycle results were included. Results: Results consistently showed that patients in sunitinib group experienced statistically significantly milder kidney-related symptoms, better cancer-specific HRQoL and general health status (in social utility scores) during the study period as measured by these patient-reported outcome end points. No statistical differences between groups were found on the FACT-G physical well-being subscale or the EQ-5D VAS values. Conclusions: Results from MEM showed the sunitinib's benefit on HRQoL compared with IFN-α.

The objective of this study was to evaluate the efficacy and safety profile of weekly docetaxel, estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer. Forty-eight patients received 35 mg m(-2) of weekly docetaxel for 3 out of every 4 weeks, 280 mg of estramustine twice daily on days 1-3, 8-10, 15-17 and 400 mg of celecoxib twice daily until progression or toxicity. Cycles were repeated every 28 days for at least six cycles. Patients were evaluated for response and toxicity. Patients received a median of four cycles (range: 1-9). On an intention-to-treat analysis, prostate-specific antigen (PSA) was decreased greater than 50% in 28 out of 48 patients (overall response rate: 58%, 95% confidence interval (CI): 44-72) and median duration of PSA response was 8.0 months (95% CI: 6.9-9.0). After a median follow-up of 11.3 months, the median time to progression was 7.1 months and the median overall survival was 19.2 months. The most frequent severe toxicity was asthenia (15% of patients), diarrhoea and stomatitis (8% of patients, each). Grade 3/4 neutropenia was reported in two patients. There was a toxic death during the study due to a gastric perforation. Celecoxib with weekly docetaxel and estramustine is an effective and safe treatment for patients with hormone-refractory prostate cancer, but it does not seem to add any benefit to docetaxel.

Background Up to 50% of patients with bladder cancer cannot be treated with cisplatin because they are considered unfit due to poor renal function. Gemcitabine and oxaliplatin are active, nonnephrotoxic therapies with nonoverlapping toxicity profiles that provide an alternative therapy for this group of patients. Patients and methods In a multicenter study, patients received gemcitabine 1200 mg/m2 on days 1 and 8 and oxaliplatin 100 mg/m2 on day 8 every 21 days. Eligible criteria were creatinine clearance >30 ml/min and/or Eastern Cooperative Oncology Group (ECOG) performance status of two or less. Results Forty-six patients were assessable for response and toxicity. Median age was 69 years (range 52–85), median ECOG two (range 0–2). Median number of metastatic sites was 2 (range 1–6). Median creatinine clearance was 50.73 ml/min (range 30–87). A total of 187 cycles were given with a median of 5 (range 1–6). Hematological toxicity was mild with grade 3–4 peripherical neuropathy occurring in 4% of patients. Overall response rate was 48% (three complete response, 19 partial response, seven stable disease and 17 progressive disease). Median time to disease progression was 5 months. Conclusion Gemcitabine–oxaliplatin is an active and tolerable combination with response rate that merits further study in patients with impaired renal function but good performance status.

Background: North American and Japanese non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) activation via tyrosine kinase (TK) mutations respond dramatically to gefitinib treatment. To date, however, the frequency and effect of EGFR TK mutations have not been examined in European patients. Patients and methods: Eighty-three Spanish advanced NSCLC patients who had progressed after chemotherapy, were treated with compassionate use of gefitinib. Patients were selected on the basis of available tumor tissue. Tumor genomic DNA was retrieved from paraffin-embedded tissue obtained by laser capture microdissection. EGFR mutations in exons 19 and 21 were examined by direct sequencing. Results: EGFR mutations were found in 10 of 83 (12%) of patients. All mutations were found in adenocarcinomas, more frequently in females (P = 0.007) and non-smokers (P = 0.01). Response was observed in 60% of patients with mutations and 8.8% of patients with wild-type EGFR (P = 0.001). Time to progression for patients with mutations was 12.3 months, compared with 3.6 months for patients with wild-type EGFR (P = 0.002). Median survival was 13 months for patients with mutations and 4.9 months for those with wild-type EGFR (P = 0.02). Conclusions: EGFR TK mutational analysis is a novel predictive test for selecting lung adenocarci

Purpose: To compare the survival benefit obtained with cisplatin plus gemcitabine, a cisplatin-based triplet, and nonplatinum sequential doublets in advanced non–small-cell lung cancer (NSCLC). Patients and Methods: Stage IIIB to IV NSCLC patients were randomly assigned to receive cisplatin 100 mg/m2 day 1 plus gemcitabine 1,250 mg/m2 days 1 and 8, every 3 weeks for six cycles (CG); cisplatin 100 mg/m2 day 1 plus gemcitabine 1,000 mg/m2 and vinorelbine 25 mg/m2 days 1 and 8, every 3 weeks for six cycles (CGV); or gemcitabine 1,000 mg/m2 plus vinorelbine 30 mg/m2 days 1 and 8, every 3 weeks for three cycles, followed by vinorelbine 30 mg/m2 days 1 and 8 plus ifosfamide 3 g/m2 day 1, every 3 weeks for three cycles (GV–VI). Results: Five hundred fifty-seven patients were assigned to treatment (182 CG, 188 CGV, 187 GV–VI). Response rates were significantly inferior for the nonplatinum sequential doublet (CG, 42%; CGV, 41%; GV–VI, 27%; CG v GV–VI, P = .003). No differences in median survival or time to progression were observed. Toxicity was higher for the triplet: grade 3 to 4 neutropenia (GC, 32%; CGV, 57%; GV–VI, 27%; P < .05); neutropenic fever (CG, 4%; CGV, 19%; GV–VI, 5%; P < .0001); grade 3 to 4 thrombocytopenia (CG, 19%; CGV, 23%; GV–VI, 3%; P = .0001); and grade 3 to 4 emesis (GC, 22%; GCV, 32%; GV–VI, 6%; P < .0001). Conclusion: On the basis of these results, CG remains a standard regimen for first-line treatment of advanced NSCLC.

To identify a novel system for scoring intratumoral immune response that can improve prognosis and therapy decisions in early stage non-small cell lung cancer (NSCLC). Eighty-four completely resected stage I/II NSCLC without adjuvant therapy were classified by expression profiling using whole genome microarrays. An external cohort of 162 tumors was used to validate the results. Immune cells present in tumor microenvironment were evaluated semiquantitatively by CD20, CD79, CD3, CD8, CD4 and CD57 immunostaining. Univariate and multivariate analyses of variables associated with recurrence-free survival were performed. Initial molecular classification identified three clusters, one with significantly better RFS. A reduced two-subgroup classification and a 50-gene predictor were built and validated in an external dataset: high and low risk of recurrence patients (HR = 3.44; p = 0.001). Analysis of the predictor´s genes showed that the vast majority were related to a B/plasma cell immune response overexpressed in the low-risk subgroup. The predictor includes genes coding for unique B lineage-specific genes, functional elements or other genes that, although non-restricted to this lineage, have strong influence on B-cell homeostasis. Immunostains confirmed increased B-cells in the low-risk subgroup. Gene signature (p

The objective of this study was to evaluate the activity, toxicity, and long-term survival of patients with locally advanced unresectable squamous cell carcinoma of the head and neck treated with neoadjuvant chemotherapy (cisplatin, 5-fluorouracil [5-FU] and leucovorin) followed by conventional radiation therapy. Twenty-six patients with stage III or IV squamous cell carcinoma of the head and neck were treated with four cycles of cisplatin 100 mg/m2, 5-FU mg/m2/day as a continuous infusion for five consecutive days, and oral leucovorin 120 mg/day for five days, administered every three weeks. After neoadjuvant treatment, patients underwent standard radiation therapy (50–70 Gy). The most remarkable toxic effects included mucositis (30.7%; grade: 3) and neutropenia (30.7%; grade: 3/4), although only one case of febrile neutropenia was recorded. Two toxic deaths were recorded. The major objective response achieved was 88.4% (23 patients), seven (26.9%) of which were complete. After local treatment, 57.7% of the patients achieved complete remission. With a mean follow-up of 50 months, the median period free of disease progression was 14 months, with a median overall survival of 20 months. The 2- and 4-year survival rates were 46.1% and 23%, respectively. In conclusion, these results seem to be no better than those reported with the traditional cisplatin plus 5-FU without leucovorin, although this issue can be clearly clarified only by carrying out randomized clinical trials.

Background: A strong rationale supports the role of antiangiogenic drugs in urothelial cancer. This trial was designed to assess the activity of sunitinib as first-line treatment in patients with metastatic urothelial cancer ineligible for cisplatin and to explore molecular and imaging variables predictive of clinical benefit. Patients and methods: This was a multicenter phase II trial with sunitinib 50 mg daily in 4/2-week schedule. Eligibility criteria were as follows: creatinine clearance 30-60 ml/min, Eastern Cooperative Oncology Group Pperformance Sstatus of one or less, and adequate hepatic and hematologic function. Twelve circulating cytokines were evaluated at baseline and sequentially using Luminex xMAP (R) (Austin, TX). Baseline and treatment-related changes in perfusion were evaluated in a patient subgroup using contrast-enhanced computed tomography. Results: On intention-to-treat analysis, 38 patients showed 3 (8%) partial responses (PRs) and 19 (50%) presented with stable disease (SD), 17 (45%) of them >= 3 months. Clinical benefit (PR + SD) was 58%. Median time to progression (TTP) was 4.8 months and median overall survival 8.1 months. Toxicity was consistent with previous reports for sunitinib. Low interleukin-8 (IL-8) baseline levels were significantly associated with increased TTP. Baseline tumor contrast enhancement with > 40 Hounsfield units was associated with clinical benefit. Conclusions: This study highlights the potential role of the angiogenic pathway as a therapy target in urothelial cancer. Baseline IL-8 serum levels and contrast enhancement of lesions warrant further study.

Background: Activating mutations in the epidermal growth factor receptor gene (EGFR) confer hypersensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in patients with advanced non-small-cell lung cancer. We evaluated the feasibility of large-scale screening for EGFR mutations in such patients and analyzed the association between the mutations and the outcome of erlotinib treatment. Methods: From April 2005 through November 2008, lung cancers from 2105 patients in 129 institutions in Spain were screened for EGFR mutations. The analysis was performed in a central laboratory. Patients with tumors carrying EGFR mutations were eligible for erlotinib treatment. Results: EGFR mutations were found in 350 of 2105 patients (16.6%). Mutations were more frequent in women (69.7%), in patients who had never smoked (66.6%), and in those with adenocarcinomas (80.9%) (P

Forty-six women with breast cancer treated with adjuvant FAC (fluorouracil, doxorubicin and cyclophosphamide) entered a multicenter, randomized, double-blind, cross-over trial in which thiethylperazine (T) (6.5 mg p.o every 8 h x 3 days) plus methylprednisolone (MP) (250 mg i.v. x 2 doses) was compared with thiethylperazine plus placebo. Forty-four patients were evaluable for efficacy. T + MP was significantly better in reducing vomiting (p less than 0.01) and nausea (p less than 0.02). The complete protection rate against vomiting was 36% for T + MP compared to 18% for T + placebo, and the percentage of nausea grades 0 + 1 (none or slight) was 59% and 27% respectively. The patient preference after cross-over was strikingly in favor of T + MP (70% versus 13%) (p less than 0.001). The most important side-effects of T + MP were facial flushing (22%) and euphoria (27%). Other side-effects, such as dryness of the mouth and sedation, were common after both treatments. In conclusion, the study suggested that T + MP is superior to T alone in protecting from nausea and vomiting induced by FAC.

J.A. Arranz Arija, B. Perez-Valderrama, J.L. Gonzalez-Larriba, A. Rodriguez Sanchez, I. Chirivella, A. Pinto, R.D. Garcia Marrero, G. Rubio, J.M. Jurado Garcia, P. Borrega, M. Lazaro Quintela, D.E. Castellano, C. Suarez Rodriguez, J.A. Meana Garcia, J.J. Lambea-Sorrosal, P. Gajate, M.J. Juan Fita, J.L. Puertas, R. Garcia Dominguez, J.C. Villa Guzman. Hospital General universitario Gregorio Maranon, Medical Oncology Service, Madrid, Spain; Hospitales Universitarios Virgen del Rocio, Medical Oncology Service, Seville, Spain; Hospital Clinico San Carlos, Medical Oncology Service, Madrid, Spain; Hospital Universitario de Leon, Medical Oncology Service, Leon, Spain; Hospital Clinico Universitario, Medical oncology Service, Valencia, Spain; Hospital Universitario La Paz, Medical Oncology Service, Madrid, Spain; Hospital Universitario de Canarias, Medical Oncology Service, Santa Cruz de Tenerife, Spain; Hospital Universitario Fundacion Jimenez Diaz, Medical Oncology Service, Madrid, Spain; Hospital Universitario San Cecilio, Medical Oncology Service, Granada, Spain; Hospital San Pedro de Alcantara, Medical Oncology Service, Caceres, Spain; Complexo Hospitalario Universitario de Vigo, Medical Oncology Service, Vigo, Spain; Hospital Universitario 12 de Octubre, Medical Oncology Service, Madrid, Spain; Hospital Universitari Vall d’Hebron, Medical Oncology Service, Barcelona, Spain; Hospital General Universitario de Alicante, Medical Oncology Service, Alicante, Spain; Hospital Universitario Lozano Blesa, Medical Oncology Service, Zaragoza, Spain; Hospital Universitario Quiron, Medical Oncology Service, Madrid, Spain; 17 Instituto Valenciano de Oncologia IVO, Medical Oncology Service, Valencia, Spain; Hospital Universitario Rio Hortega, Medical Oncology Service, Valladolid, Spain; Hospital Universitario de Salamanca, Medical Oncology Service, Salamanca, Spain; Hospital General Universitario de Ciudad Real, Medical Oncology Service, Ciudad Real, Spain

e11616 Background: In November 2013 the American Society of Clinical Oncology (ASCO) and the College of American Pathologists updated the guidelines for determining HER2 status in order to improve ...

e15597 Background: The IMRCC prognostic model for mRCC treated with VEGF-targeted agents (Heng, JCO '09) has been externally validated (Heng, Lancet Oncol '13), however, pt treated with Pz were not...

Background A recently published study shows that ERL and chemotherapy (MTA/docetaxel) offer similar efficacy outcomes in pretreated patients (p) with advanced NSCLC, and a direct comparison of ERL versus MTA in a prospective, randomized phase III trial also shows equivalent efficacy. However, both studies were conducted before the treatment-by-histology interaction effect was observed for MTA and p were not prospectively selected based on histology. Moreover, both studies included p considered optimal candidates for randomized trials, not always representative of the entire patient population. Material and methods P with advanced nsNSCLC treated with ERL (150 mg/d p.o.) or MTA (500 mg/m2 on d1, every 3 weeks) as 2nd-line treatment were included in the study. This single-centre, retrospective, observational study was conducted to compare the efficacy and safety of ERL versus MTA in non-selected p with nsNSCLC who have progressed after 1st-line chemotherapy in a clinical practice scenario. Results From 2006-2011, 67 p fulfill eligibility criteria, ERL (n = 32) and MTA (n = 35). Baseline characteristics ERL/MTA: median age 67/65 yrs.; male 69/80%; smokers 34/40%; PS ≥ 2 22/26%; adenocarcinoma 91/71%; stage IV 81 /77%; EGFR mutation positive 19/3%. No difference in terms of OS, 8.9 m (ERL) vs 7.1 months (MTA) (p = 0.551). Statistically significant differences were recorded for PFS, 3.5 (ERL) and 2.3 months (MTA) (p = 0.02) and a relative reduction in risk of progression of 53.5 % for ERL vs MTA (p = 0.005). SLP differences remained statistically significant when adjusting for EGFR mutation status, histology, prior response to 1st-line treatment and location of metastatic sites. OS showed a non-statistically significant difference after adjusting for each variable. The DCR was 40.6% in the ERL and 31.4 % in the MTA arm (p = 0.46). There was more grade 3-4 hematologic toxicity, anemia (8.5%), thrombopenia (11.4 %) and neutropenia (5.71%), in the MTA arm, and skin rash (9.3%) and diarrhea (6.2%) in the ERL arm. Conclusions These results in real-life setting suggest that ERL offers similar efficacy outcomes as MTA for p with nsNSCLC, with less and easier manageable toxicity. Disclosure All authors have declared no conflicts of interest.

e15053 Background: There is no standard treatment of 2L for mGC. Irinotecan has been shown to increase overall survival (OS) in this setting. FOLFIRI is an active and well-tolerated regimen which h...

Transitional cell carcinoma (TCC) of the urothelium is a highly chemosensitive tumour. Combination chemotherapy can provide both palliation and a modest survival advantage in patients with advanced disease. At present, the combination of cisplatin, methotrexate, doxorubicin and vinblastine (M-VAC) is the most widely used for advanced TCC with an overall response rate of 40-72% in phase II, and 35-45% in phase III studies, and a median survival of approximately 12 months. These modest results and the unsuccessful attempts to increase efficacy with dose intensive M-VAC schedules have prompted the identification of new active agents in TCC, such as the taxanes and gemcitabine. The overall response rates for two-drug regimens of cisplatin-paclitaxel, carboplatin-paclitaxel and cisplatin-gemcitabine range from 63 to 72%, 14 to 65% and 42 to 66%, respectively. The overall response rates for platinum-paclitaxel-gemcitabine three-drug regimens range from 58 to 80%. The potential clinical benefit of these new three-drug combinations in the treatment of TCC needs to be tested in future phase III studies.