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PURPOSE Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) demonstrated survival benefit versus bevacizumab, carboplatin, and paclitaxel (BCP) in chemotherapy-naïve nonsquamous non–small-cell lung cancer (NSCLC). We present safety and patient-reported outcomes (PROs) to provide additional information on the relative impact of adding atezolizumab to chemotherapy with and without bevacizumab in nonsquamous NSCLC. METHODS Patients were randomly assigned to receive atezolizumab, carboplatin, and paclitaxel (ACP), ABCP, or BCP. Coprimary end points were overall survival and investigator-assessed progression-free survival. The incidence, nature, and severity of adverse events (AEs) were assessed. PROs, a secondary end point, were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core 30 and EORTC QLQ-Lung Cancer 13. RESULTS Overall, 400 (ACP), 393 (ABCP), and 394 (BCP) patients were safety evaluable (ie, intention-to-treat population that received one or more doses of any study treatment). More patients had grade 3/4 treatment-related AEs during the induction versus maintenance phase (ACP, 40.5% v 8.2%; ABCP, 48.6% v 21.2%; BCP, 44.7% v 11.1%). During induction, the incidence of serious AEs (SAEs) was 28.3%, 28.5%, and 26.4% in the ACP, ABCP, and BCP arms, respectively. During maintenance, SAE incidences were 20.0%, 26.3%, and 13.0%, respectively. Completion rates of the PRO questionnaires were > 88% at baseline and remained ≥ 70% throughout most study visits. Across arms, patients on average reported no clinically meaningful worsening of global health status or physical functioning scores through cycle 13. Patients across arms rated common symptoms with chemotherapy and immunotherapy similarly. CONCLUSION ABCP seems tolerable and manageable versus ACP and BCP in first-line nonsquamous NSCLC. Treatment tolerability differed between induction and maintenance phases across treatment arms. PROs reflect a minimal treatment burden (eg, health-related quality of life, symptoms) with each regimen.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations, Background There is a lack of useful diagnostic tools to identify EGFR mutated NSCLC patients with long-term survival. This study develops a prognostic model using real world data to assist clinicians to predict survival beyond 24 months. Methods EGFR mutated stage IIIB and IV NSCLC patients diagnosed between January 2009 and December 2017 included in the Spanish Lung Cancer Group (SLCG) thoracic tumor registry. Long-term survival was defined as being alive 24 months after diagnosis. A multivariable prognostic model was carried out using binary logistic regression and internal validation through bootstrapping. A nomogram was developed to facilitate the interpretation and applicability of the model. Results 505 of the 961 EGFR mutated patients identified in the registry were included, with a median survival of 27.73 months. Factors associated with overall survival longer than 24 months were: being a woman (OR 1.78); absence of the exon 20 insertion mutation (OR 2.77); functional status (ECOG 0–1) (OR 4.92); absence of central nervous system metastases (OR 2.22), absence of liver metastases (OR 1.90) or adrenal involvement (OR 2.35) and low number of metastatic sites (OR 1.22). The model had a good internal validation with a calibration slope equal to 0.781 and discrimination (optimism corrected C-index 0.680). Conclusions Survival greater than 24 months can be predicted from six pre-treatment clinicopathological variables. The model has a good discrimination ability. We hypothesized that this model could help the selection of the best treatment sequence in EGFR mutation NSCLC patients.

e23135 Background: Breakthrough cancer pain (BTcP) is one of the most common symptoms related with the disease and its treatment. Its management differs from that of chronic pain but there is not a wide consensus about fundamental aspects of BTcP definition, diagnosis, follow-up, and management. The objective of this study promoted by ECO Foundation, is to reach a consensus on the follow-up of patients with BTcP under opioid treatment. Methods: This work was conducted using a modified Delphi method organized in two rounds and involving a panel of 84 medical oncologists. A questionnaire of 66 items was developed. The items proposed to reach a consensus included the following topics: 1) When to perform the first and subsequent BTcP treatment evaluations; 2) What to assess at the first follow-up visit and how; and 3) What to assess in the following visits and how. Results: After two rounds, a consensus was reached on 80.3% of the items proposed. The main agreements reached include: The first follow-up visit should preferably be face-to-face; increase the number of visits after detecting poor control of BTcP; assess pain control episodes of BTcP in the first and following visits; adjust treatment dose of opioids due to poor control of BTcP; and adopt measures to prevent aberrant opioid-induced behaviors when treating BTcP in patients with cancer. Conclusions: This Delphi consensus highlights the different points of view of medical oncologists regarding the follow-up of patients with BTcP under opioids treatment. Nonetheless, the conclusions reached can facilitate optimizing monitoring of these patients and promote long-term effectiveness of BTcP control.

Objectives The aim of LungBEAM was to determine the value of a novel epidermal growth factor receptor (EGFR) mutation test in blood based on BEAMing technology to predict disease progression in advanced non‐small cell lung cancer (NSCLC) patients treated with first‐ or second‐generation EGFR‐tyrosine kinase inhibitors (EGFR‐TKIs). Another goal was to monitor the dynamics of EGFR mutations, as well as to track EGFR exon 20 p.T790M (p.T790M) resistance during treatment, as critical indicators of therapeutic efficacy and patient survival. Methods Stage IV NSCLC patients with locally confirmed EGFR‐TKI sensitizing mutations (ex19del and/or L858R) in biopsy tissue who were candidates to receive first‐ or second‐generation EGFR‐TKI as first‐line therapy were included. Plasma samples were obtained at baseline and every 4 weeks during treatment until a progression‐free survival (PFS) event or until study completion (72‐week follow‐up). The mutant allele fraction (MAF) was determined for each identified mutation using BEAMing. Results A total of 68 of the 110 (61.8%) patients experienced a PFS event. Twenty‐six patients (23.6%) presented with an emergent p.T790M mutation in plasma at some point during follow‐up, preceding radiologic progression with a median of 76 (interquartile ratio: 54–111) days. Disease progression correlated with the appearance of p.T790M in plasma with a hazard ratio (HR) of 1.94 (95% confidence interval [CI], 1.48–2.54; p, The manuscript is a multicenter, prospective study conducted in the real‐world setting. The study reveals that the detection and quantification (MAF slope) of EGFR mutations in ctDNA using the highly sensitive BEAMing method may assist in optimizing treatment decisions for advanced NSCLC patients.

Background: Little progress has been achieved in non-small cell lung cancer (NSCLC) patients with unresectable stage III disease and new drug schemes are warranted. Material and methods: In this open-label, single-arm, phase II trial 65 treatment-naive stage III NSCLC deemed surgically unresectable by a multidisciplinary team were treated with 2 cycles of induction cisplatin at 80 mg/m(2) every 21 days plus metronomic oral vinorelbine at 50 mg/day every Monday, Wednesday and Friday. During the concomitant treatment with thoracic radiotherapy cisplatin was administered in the same manner but oral vinorelbine was reduced to 30 mg/day. The objective was to administer a total radiotherapy dose of 66 Gy in 33 daily fractions of 2 Gy. The primary endpoint was progression-free survival (PFS). Correlation between circulating tumor DNA (ctDNA) levels and survival was also evaluated. Results: Fifty-five (78.5 %) patients completed treatment. Overall response rate, by RECIST criteria, was 66.2 %. Four (6.2 %) patients had complete response, 39 (60.0 %) partial response and 12 (18.5 %) stable disease. Seven patients (10.8 %) had progressive disease during the induction period. Median follow-up was 29.1 months (m), median PFS was 11.5 m (95 %CI: 9.6-15.4). PFS at 12 m in the intention-to-treat (ITT) population was 47.8 % (95 %CI: 35.1-59.4 %) and median OS was 35.6 m (95 %CI: 24.4-46.8). Grade >= 3 treatment-related adverse events occurred in 14 (21.5 %) patients during induction and in 13 (24.5 %) patients during concomitant treatment with esophagitis occurring in 3% and pneumonitis in 1.5 % of the patients. Patients with undetectable ctDNA after 3 m follow-up had median PFS and OS of 18.1 m (95 %CI: 8.8-NR) and not reached (NR) (95 %CI: 11.3-NR), respectively, compared with 8.0 m (95 %CI: 2.7-NR) and 24.7 m (95 %CI: 5.7-NR) for patients who remained ctDNA positive at that time point. Conclusions: Metronomic oral vinorelbine and cisplatin obtains similar efficacy results with significantly lower toxicity than the same chemotherapy at standard doses. ctDNA can identify populations with particularly good prognosis.

BACKGROUND: Biological differences between the sexes have a major impact on disease and treatment outcome. In this paper, we evaluate the prognostic value of sex in stage IV non-small-cell lung cancer (NSCLC) in the context of routine clinical data, and compare this information with other external datasets. METHODS: Clinical data from stage IV NSCLC patients from Hospital Puerta de Hierro (HPH) were retrieved from electronic health records using big data analytics (N = 397). In addition, data from the Spanish Lung Cancer Group (GECP) Tumor Registry (N = 1382) and from a published study available from the cBioPortal (MSK) (N = 601) were analyzed. Survival curves were estimated using the Kaplan-Meier method. A Cox proportional hazards regression model was used to assess the prognostic value of sex. A meta-analysis to compare the outcome for males and females in terms of overall survival (OS) and progression free survival (PFS) was performed. RESULTS: The median OS time was 12 months for males and 19 months for females (overall HR = 0.77; 95% CI: 0.68-0.87; P < 0.001). Similarly, females with stage IV NSCLC harboring an EGFR-sensitizing mutation lived significantly longer than males (median OS: males, 19 months; females, 32 months) with a lower risk of death compared with males (overall HR = 0.75; 95% CI: 0.67-0.84). In addition, female patients benefited more from EGFR inhibitors in terms of PFS and OS (overall HR = 0.45; 95% CI: 0.32-0.64, and HR = 0.62; 95% CI: 0.48-0.80, respectively). Median PFS was 21 months in females and 12 months in males (P < 0.001). CONCLUSIONS: Using routine clinical data we confirmed the previous finding that among stage IV NSCLC patients, females had a significantly better prognosis than males. The effect size of the sex was notable, highlighting the fact that survival rates are usually estimated and patients are generally managed without considering the sexes separately, which may lead to suboptimal results.

Renal cell cancer has been rarely reported as a cause of gastric or esophageal metastases. They usually present with gastrointestinal bleeding and most cases have been managed surgically or endoscopically. We report the case of a 38-year-old man with a 4-year history of metastatic renal cell carcinoma admitted to the emergency room with melena and anemia. At endoscopy, three esophageal polypoid lesions (middle and distal thirds) and a 7 cm mass in the gastric fundus were identified. Biopsy revealed esophageal mucosa infiltrated by renal cell carcinoma. Radiotherapy was administered (30 Gy in 10 fractions), followed by pazopanib, with excellent tolerance and without new bleeding episodes. Computed tomography scan showed complete disappearance of the esophageal and fundic lesions at 3 months follow-up. Twenty-four months after being initiated on pazopanib, there is no radiological evidence of disease. This is the first reported case showing complete remission of gastric and esophageal metastases after treatment with radiotherapy and pazopanib.

One of the most important advances in the treatment of non-small cell lung cancer (NSCLC) has been the identification of molecular alterations vulnerable to targeted inhibition, such as mutations in the epidermal growth factor receptor (EGFR) gene. EGFR tyrosine kinase inhibitors (EGFR-TKIs) are targeted agents used to treat EGFR mutation-positive advanced NSCLC showing significant improvements in terms of response rate (RR) and progression-free survival (PFS) compared to conventional chemotherapy. However, all patients eventually develop resistance to first-line EGFR-TKIs. The most common mechanism of acquired resistance is the secondary acquisition of a single missense mutation within exon 20 in the EGFR gene, known as the T790M mutation (49-60%). New agents targeting the T790M mutation have undergone clinical development, and among these, osimertinib has shown significant activity in relapsing EGFR mutation positive patients harbouring the T790M mutation. Although precision medicine is a reality for NSCLC, obtaining relevant tissue for repeated molecular analysis from these patients remains a challenge. In this article, a group of experts from the Spanish Society of Medical Oncology (SEOM) and the Spanish Lung Cancer Group (GECP) evaluated the role of rebiopsy and the potential application of plasma-testing methodologies in advanced EGFR mutation patients progressing after EGFR-TKI.

Renal cell carcinoma (RCC) is a complex disease characterized by mutations in several genes. Loss of function of the von Hippel-Lindau (VHL) tumour suppressor gene is a very common finding in RCC and leads to up-regulation of hypoxia-inducible factor (HIF)-responsive genes accountable for angiogenesis and cell growth, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Binding of these proteins to their cognate tyrosine kinase receptors on endothelial cells promotes angiogenesis. Promotion of angiogenesis is in part due to the activation of the phosphatidylinositol-3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) pathway. Inhibition of this pathway decreases protein translation and inhibits both angiogenesis and tumour cell proliferation. Although tyrosine kinase inhibitors (TKIs) stand as the main first-line treatment option for advanced RCC, eventually all patients will become resistant to TKIs. Resistance can be overcome by using second-line treatments with different mechanisms of action, such as inhibitors of mTOR, c-MET, programmed death 1 (PD-1) receptor, or the combination of an mTOR inhibitor (mTORi) with a TKI. In this article, we briefly review current evidence regarding mechanisms of resistance in RCC and treatment strategies to overcome resistance with a special focus on the PI3K/AKT/mTOR pathway.

The speed at which targeted therapies are being developed and incorporated into the treatment of advanced renal cell carcinoma (RCC) is surprising. After decades in which the only systemic treatment options available for advanced disease were interleukin-2 and interferon-alpha, in the last decade, six new targeted therapies have emerged showing meaningful clinical benefits to patients with advanced RCC through phase III trials. Recently, the Spanish Oncology Genitourinary Group issued its first public statement of recommendations for the optimal management of advanced RCC. However, most pivotal phase III trials on which these recommendations were based have been updated and/or fully reported. Moreover, a new multikinase inhibitor, pazopanib, has emerged with good quality clinical data. In this report, we review in depth the latest phase III data of targeted therapies for advanced RCC and update our recommendations. Furthermore, we hypothesize about the best environment for patients with advanced RCC to receive cancer therapy.

8537Background: 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 effic...

623 Background: Treatment of mRC is not affected by gender, studying possible differences in a real-world study, could increase the knowledge of toxicity and possible prognostic factors. Methods: SPAZO2 (NCT03091465) was a retrospective real-world study to analyze the effectiveness of 1st-line pazopanib and subsequent therapies in mRC. Data from 530 pt treated outside CT were collected in 50 spanish centers, and externally monitored. Ineligibility criteria: ECOG > 1, pure nonclear-cell, Hgb < 9 g/dl, renal failure, severe cardiovascular disease, chronic liver disease, or recent neoplasia Results: 530 pt were included, 67.2% men (M), mean age was 66.2 years (26-92). There were no significant differences (M vs W) in the age > 75 (24.7 vs 24.1%), clear cell carcinoma (77.2 vs 79.9%), nephrectomy (72.5 vs 68.4%), IMDC (favourable: 15.2 vs 12.1%, intermediate: 59.3 vs 64.4%, poor: 25.6 vs 23.6%), metastases (lymph nodes: 46.1 vs 43.1%, lung: 69,7 vs 67,2 %, liver: 16 vs 20.1%, bone: 27 vs 24.1%, skin/soft tissues: 1.1 vs 3,4% and CNS: 4,8% vs 6.3%). Discontinuation due to toxicity or comorbidities was 12.4 vs 9.8%. There were no differences in the second lines received (57.9 vs 56.9%), neither response, PFS and OS (table). Median follow up was 39 mo. The gender has no prognostic value when adjusted for the prognostic groups of IMDC (HR of PFS 0.96, CI 95% 0.78-1.2, HR of OS: 0.92, CI 95% 0.72-1.14). Only diarrhea and elevation of uric acid were higher in the men group. Conclusions: Pazopanib was safe and effective in both groups with similar outcome. Women had less diarrhea and less increased uric acid. There were not differences in OS or PFS. In IMDC subgroup analysis, there is a trend towards a better evolution or PFS in the poor prognosis women subgroup. Clinical trial information: NCT03091465. [Table: see text]

A retrospective analysis based on the Spanish Lung Cancer Group (SLCG) clinical trial of high-dose epirubicin/cisplatin in patients with small-cell lung cancer (SCLC) was performed. Patients younger than 70 years vs. older than 70 years old were analyzed to evaluate the influence of age on response to treatment, toxicity, time to progression (TTP) and overall survival (OS) of the chemotherapy schedule. Three hundred and thirty eight patients70 years and sixty-four70 years, were analyzed. Objective responses were similar in both groups. In patients less than 70 years higher TTP (36 weeks vs. 32 weeks) and OS (47 weeks vs. 42 weeks) were seen, attributable to the improved results observed in the subgroup of patients with limited disease (LD). No significant differences were observed when toxicity profile of both groups was compared, except for a higher rate of febrile neutropenia observed in the elderly group with extensive disease (4.6% vs. 8.8%, p=0.01). In the subgroup of patients with LD, elderly patients received less total cisplatin dose (401 vs. 508 mg/m(2), p=0.01) although less treatment delays were reported (10 days vs. 15 days, p=0.05). Age was likely to be a negative prognostic factor for OS of elderly patients with LD. It also seemed to be related to a greater dose reduction, which may explain that toxic episodes and delays occurred more frequently in the younger patients receiving the full scheduled dose. However, the definitive reason to explain this could not be established due to the characteristics of our analysis.

The presence of single nucleotide polymorphisms (SNPs) in DNA repair genes, such as xeroderma pigmentosum group D (XPD), can impair DNA repair capacity, thereby affecting chemotherapy efficacy and clinical outcome of patients. Assessment of XPD polymorphisms can permit better stratification of patients into more refined risk categories and optimize decision-making for multidisciplinary treatment in locally advanced nonsmall cell lung cancer (NSCLC). Objective: The aim of this study was to evaluate whether xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunit M1 (RRM1) polymorphisms influenced clinical outcome in patients with stage IIIA-B nonesmall-cell lung cancer (NSCLC) treated with neoadjuvant gemcitabine/cisplatin/docetaxel followed by surgery. Materials and Methods: A total of 109 patients with stage IIIA and IIIB NSCLC were prospectively genotyped to examine a potential association between XPD 312 (aspartic acid [Asp]/asparagine [Asn]), XPD 751 (lysine [Lys]/glutamine [Gln]), and RRM1 (-37 C/A) polymorphisms with response and survival. Results: The median survival was 32.14 months for carriers of XPD 312 Asp/Asp and 12.04 months for those with the variant Asn allele (P = .05). In addition, event-free survival was longer for patients with the XPD 312 Asp/Asp genotype compared with patients with Asp/Asn or Asn/Asn (P = .03). A similar but nonsignificant trend was observed for the XPD 751 genotype. In a multivariate analysis, complete resection and age emerged as prognostic factors for overall survival; in patients with incomplete resection or exploratory thoracotomy, XPD 312 was the most significant prognostic factor (P = .03). Conclusion: The XPD 312 single nucleotide polymorphism is a prognostic factor for survival in patients with locally advanced NSCLC receiving induction.

Preoperative chemotherapy has become an accepted treatment for stage IIIA (N2) non–small-cell lung cancer (NSCLC). The majority of induction regimens employ cisplatin, although the importance of cisplatin dose in combination is unclear. A randomized trial was conducted to address whether higher preoperative cisplatin doses result in improved survival and increased pathologic complete response in NSCLC. Patients with stage IIIA clinically enlarged and biopsy-proven N2 lesions were randomly assigned to receive either high-dose cisplatin (HDCP) (100 mg/m 2 ) or moderate-dose cisplatin (MDCP) (50 mg/m 2 ) in combination with ifosfamide (3 g/m 2 ) and mitomycin (6 mg/m 2 ). Disease was restaged after 3 cycles, and those patients with response or stable disease underwent thoracotomy. From March 1993 to February 1997, 83 patients were randomized: 46 received HDCP, and 37 received MDCP. Clinical characteristics were well matched. Radiographic response rate was 59% for HDCP patients and 30% for MDCP patients ( P = 0.01). Thoracotomy was performed in 71 patients (86%), 58 of whom had resectable disease. Complete resection rate was 61% in the HDCP group, and 51% in the MDCP group ( P = 0.5). Postoperative mortality was 11%. Pathologic complete response was observed in one patient who received MDCP. Median survival in the HDCP and MDCP groups was 13 and 11 months, respectively ( P = 0.3). In conclusion, higher radiographic response rate is observed in patients who receive HDCP, but this study fails to show any significant improvement in either overall survival or pathologic complete response in this group of patients.

[EN] Background: In advanced-stage (IIIB or IV) non-small-cell lung cancer (NSCLC), combination chemotherapy has demonstrated response rates of 20% and a 1-year survival rate of 30%. We conducted a multicentre, open-label, nonrandomised phase II trial to determine the efficacy and tolerability of sequential monotherapy with gemcitabine followed by paclitaxel in chemotherapy-naïve patients with advanced NSCLC. Materials and methods: Between December 2002 and July 2004, the Spanish Lung Cancer Group (SLCG) conducted a study in which 34 patients with advanced (stage IIIB or IV) NSCLC received 1200 mg/m2 of i.v. gemcitabine on days 1, 8 and 15 of each 28-day cycle for a total of 3 cycles followed by 100 mg/m2 of weekly i.v. paclitaxel for a maximum of 8 weeks. If objective response or stable disease was achieved, 70 mg/m2 of weekly i.v. paclitaxel was maintained until disease progression was evident or toxic effects were intolerable. Lung Cancer Symptom Scale (LCSS) analysis was performed. Baseline levels of serum VEGF, EGFR, telomerase reverse transcriptase (hTERT) and K-ras mutations were analysed. The primary endpoint was the objective response rate. Results: The median age of the 34 patients who were enrolled was 67 years (range 46-77), but later 8 patients were excluded; 78.8% were men, 81.8% had performance status 1 and also 81.8% had metastatic disease at diagnosis. The objective response rate was 28% (95% CI, 14.2-47.8); the median overall survival was 7.2 months (95% CI, 2.1-12.3) and the median time to progression (TTP) was 3.1 months (95% CI, 2.5-5.3). Grade 3 or 4 drug-related haematological toxicities were observed in 6 patients. Patients with lower baseline serum VEGF levels had significantly longer survival. Conclusions: Sequential therapy with gemcitabine followed by paclitaxel was well tolerated with a low proportion of grade 3 or 4 adverse events, the absence of unexpected toxicity and with an improvement in quality of life. Unfortunately, the response rate did not meet the minimally required rate of 20% and the study was prematurely closed. VEGF was identified as a poor prognostic factor for TTP and survival. © 2011 Feseo.

The purpose of the Spanish Lung Cancer Anaemia Survey (SLCAS) was to thoroughly investigate lung cancer-associated anaemia management, and describe the profile of lung cancer patients in relation to anaemia incidence and tumour type in Spain.This survey collected data from 1089 randomly recruited patients gathered by 50 Spanish physicians at 38 sites. In addition, a qualitative assay was performed through 16 one-to-one and 2 one-to-two interviews, and a discussion group of 4 cancer specialists participating in the survey.Lung cancer patients undergoing chemotherapy treatment had haemoglobin (Hb) levels12.0 g/dl in 58.0% of the cases, in contrast to 39.0% of patients receiving no chemotherapy. Anaemia was treated in 53.0% of patients with Hb12 g/dl (45.0% epoetin, 3.9% transfusion, 4.1% iron). Mean Hb level trigger was 9.7 g/dl for administration of epoetin and 8.2 g/dl for blood transfusion.SLCAS reveals a significant change in the management of anaemia and clinical practice pattern in the use of erythropoiesis-stimulating agents (45.0% vs. 18.0%) and much less use of blood transfusions (3.9% vs. 15.0%) since the European Cancer Anaemia Survey performed five years ago.

Background Immunohistochemistry (IHC) with mutation-specific antibodies may be an ancillary method of detecting EGFR mutations in lung cancer patients. Methods EGFR mutation status was analyzed by DNA assays, and compared with IHC results in five non-small-cell lung cancer (NSCLC) cell lines and tumor samples from 78 stage IV NSCLC patients. Results IHC correctly identified del 19 in the H1650 and PC9 cell lines, L858R in H1975, and wild-type EGFR in H460 and A549, as well as wild-type EGFR in tumor samples from 22 patients. IHC with the mAb against EGFR with del 19 was highly positive for the protein in all 17 patients with a 15-bp (ELREA) deletion in exon 19, whereas in patients with other deletions, IHC was weakly positive in 3 cases and negative in 9 cases. IHC with the mAb against the L858R mutation showed high positivity for the protein in 25/27 (93%) patients with exon 21 EGFR mutations (all with L858R) but did not identify the L861Q mutation in the remaining two patients. Conclusions IHC with mutation-specific mAbs against EGFR is a promising method for detecting EGFR mutations in NSCLC patients. However these mAbs should be validated with additional studies to clarify their possible role in routine clinical practice for screening EGFR mutations in NSCLC patients.

Elderly or frail patients are often excluded from clinical trials. As a result, clinical outcome of these patients may differ from those obtained in trials. This situation may also hold true for patients who have severe concomitant diseases such as renal, hepatic, or cardiac dysfunction. Being aware of the wide range of clinical situations that a specialist may face is important to ensure that under any circumstances, the patient will receive the best treatment possible. The Spanish Oncology Genitourinary Group issued its first public statement on recommendations for the optimal management of advanced renal cell carcinoma (RCC). However, some issues remained unsolved. In this report, we discuss the current role of Medical Oncology in the treatment of patients with advanced RCC and review the management of special patient populations, such as elderly or patients with concomitant diseases.

For almost the last two decades, interleukin-2 and interferon-alpha have been the only systemic treatment options available for metastatic renal cell carcinoma. However, in recent years, five new targeted therapies namely sunitinib, sorafenib, temsirolimus, everolimus and bevacizumab have demonstrated clinical activity in these patients. With the availability of new targeted agents that are active in this disease, there is a need to continuously update the treatment algorithm of the disease. Due to the important advances obtained, the Spanish Oncology Genitourinary Group (SOGUG) has considered it would be useful to review the current status of the disease, including the genetic and molecular biology factors involved, the current predicting models for development of metastases as well as the role of surgery, radiotherapy and systemic therapies in the early- or late management of the disease. Based on this previous work, a treatment algorithm was developed.

In recent years platinum-based chemotherapy has become the standard of care for patients with good performance status after complete resection in stages IB-IIIA non-small-cell lung cancer (NSCLC), although the benefit is mainly in stages II and IIIA.In a retrospective trial we evaluate the clinical efficacy and toxicity profile of a platinum- and taxanes-based adjuvant chemotherapy in completely resected IB-IIIA NSCLC. The primary end point was relapse- free survival (RFS); principal secondary end points were overall survival (OS) and safety of the regimen. Potential predictive factors of efficacy and clinical patterns of relapse were also analysed.From January 2003 to December 2006, 41 patients met the inclusion criteria and were evaluable. Median age at diagnosis was 68.1 years (CI 95% 54-72; range 45-78). Most patients were males (87.7%) and had an Eastern Cooperative Oncology Group performance status score (PS) of 0-1 (87.8%), and 53.6% had adenocarcinomas. Pathological stages were as follow: 48.7% stage IB, 24.3% stage II and 26.8% stage IIIA. 75.6% of patients underwent a lobectomy and mediastinal lymphadenectomy and were treated with a combination of carboplatin AUC6 and paclitaxel 200 mg/m2 (85.36%) for 3 or 4 cycles. With a median follow-up of 18.2 months (range 5.1-46.5), 26 patients (63%) were free of disease and 32 of them were alive (78%). Median RFS was 12.1 months (CI 95% 9.8-14.9) and median OS had not been reached at the time of analysis. Patients with PSor =1 at diagnosis had a higher RFS [p=0.051 (CI 95% 0.90-0.96)]. Toxicity was generally mild and haematologic events were the most frequent. Non-haematologic toxic effects of chemotherapy were asthenia/ anorexia (12.2%), nausea/vomiting (12.2%) and peripheral neuropathy (17%), but severe toxic effects (grade 3 or greater) were uncommon (10%). We did not observe treatment-related deaths.Platinum-taxane-based adjuvant chemotherapy in IB-IIIA NSCLC following complete resection is feasible, well tolerated and can be delivered in most patients in the adjuvant setting. Ongoing molecular studies may have value in determining which patients will benefit from adjuvant chemotherapy.

Purpose To assess the activity of induction chemotherapy followed by surgery in stage IIIA and selected stage IIIB non–small-cell lung cancer patients. Patients and Methods Mediastinoscopy proof of either positive N2 (IIIA) or T4N0-1 (IIIB) disease was required. Induction therapy was three cycles of cisplatin/gemcitabine/docetaxel, followed by surgery. Results From December 1999 to March 2003, 136 patients were entered onto the study; the clinical response rate in 129 assessable patients was 56%. The overall complete resection rate was 68.9% of patients eligible for surgery (72% of stage IIIA patients and 66% of stage IIIB patients) and 48% of all assessable patients. Eight (12.9%) of 62 completely resected patients had a pathologic complete response. Seven patients (7.8%) died during the postoperative period. The median overall survival time was 15.9 months, 3-year survival rate was 36.8%, and 5-year survival rate was 21.1%, with no significant differences in survival between stage IIIA and stage IIIB patients. Median survival time was 48.5 months for 62 completely resected patients, 12.9 months for 13 incompletely resected patients, and 16.8 months for 15 nonresected patients (P = .005). Three- and 5-year survival rates were 60.1% and 41.4% for completely resected patients, 23.1% and 11.5% for incompletely resected patients, and 31.1% and 0% for nonresected patients, respectively. In the multivariate analysis, complete resection (hazard ratio [HR] = 0.35; P < .0001), clinical response (HR = 0.32; P < .0001), and age younger than 60 years (HR = 0.64; P = .027) were the most powerful prognostic factors. Conclusion Induction chemotherapy followed by surgery is effective in stage IIIA and in selected stage IIIB patients attaining complete resection.

7507 Background: Postop platinum-based CT improves outcomes in resected NSCLC with N+ (St II-IIIA). Analysis of expression of genes involved in DNA repair could be used to individualize optimal CT....

Malignant melanoma is the most rapidly increasing cancer in the world. Metastatic disease occurs in 20% of patients, and prognosis in these cases is poor. We report the case of a woman who presented breast metastasis as the first sign of recurrence of a melanoma.

e16074 Background: There is a need to find feasible clinical or biochemical markers that may help us to select pts who will get benefit from AA in the pre- and post- CT setting of mCRPC. Methods: W...

e18055 Background: B plus CT followed by mtc B has been shown to improve outcomes in patients (pts) with nsNSCLC. In the clinical setting, some pts are able to receive prolonged mtc treatment (Tx) with B. The aim of our research was to explore their clinical characteristics, in order to assess the behavior of these pts who benefit most from B. Methods: In 30 Spanish institutions we studied retrospectively data from 104 pts with advanced nsNSCLC receiving long-time mtc B defined by a PFS ≥ 9 months (m), which represents an increase in PFS of approximately 50%, as compared with historical data. Clinical and histological characteristics, Tx received, ORR, median PFS and OS, and safety data were recorded. Results: Pts characteristics: median age 57 years (yr); caucasian: 98%; ECOG PS 0/1/2 (%): 61/38/2; male: 61%; current/former/never smokers (%): 36/45/19; baseline hypertension (HTN)/cardiovascular disease (%): 24/9; adenocarcinoma: 82%; stage IV: 84%; 84% of pts presented ≤2 metastatic sites; central tumor location: 30%; tumor cavitation: 4%; among 40 pts tested, 8% presented activating EGFR mutations. 1L CT was: carboplatin/cisplatin doublets (%): 57/43; median no. of cycles for CT/B and mtc B was 6 and 18, respectively. Median B dose was 7.5 mg/kg. ORR: 83%. Of 71% of pts who had evidence of PD to 1L, 90% received second-line (2L) Tx. 77% of pts who progressed to 2L, received a third-line (3L). B was maintained in 26% and 24% of pts receiving 2L and 3L. Median PFS: 15 m (CI 95%:14-16); median OS: 31 m (95% CI: 22-39). 1 and 2 yrs survival rates (%): 97 (95% CI: 93 - 100) and 62 (95% CI: 51 - 73). Most frequent B related toxicities (%): gr 1/2 epistaxis (22/0), gr 1/2 HTN (12/6), grade 1/2/3 asthenia (2/6/4) and gr 1/2/3 proteinuria (3/3/1). Conclusions: To our knowledge, these are the first data reported of long-term survivors with advanced nsNSCLC treated with 1L CT/B plus long-time mtc B. Although prospective evaluation is required, the outstanding median OS (31 m) and 2-yr survival (62%) point out the importance of selecting Tx and the role of mtc B after 1LB. B was very well tolerated, without significant life-threatening toxicities. Subgroup analyses will be presented.

PURPOSE: We conducted a randomized trial to compare gemcitabine-cisplatin with etoposide-cisplatin in the treatment of patients with advanced non–small-cell lung cancer (NSCLC). The primary end point of the comparison was response rate. PATIENTS AND METHODS: A total of 135 chemotherapy-naive patients with advanced NSCLC were randomized to receive either gemcitabine 1,250 mg/m2 intravenously (IV) days 1 and 8 or etoposide 100 mg/m2 IV days 1 to 3 along with cisplatin 100 mg/m2 IV day 1. Both treatments were administered in 21-day cycles. One hundred thirty-three patients were included in the intent-to-treat analysis of response. RESULTS: The response rate (externally validated) for patients given gemcitabine-cisplatin was superior to that for patients given etoposide-cisplatin (40.6% v 21.9%; P = .02). This superior response rate was associated with a significant delay in time to disease progression (6.9 months v 4.3 months; P = .01) without an impairment in quality of life (QOL). There was no statistically significant difference in survival time between both arms (8.7 months for gemcitabine-cisplatin v 7.2 months for etoposide-cisplatin; P = .18). The overall toxicity profile for both combinations of drugs was similar. Nausea and vomiting were reported more frequently in the gemcitabine arm than in the etoposide arm. However, the difference was not significant. Gemcitabine-cisplatin produced less grade 3 alopecia (13% v 51%) and less grade 4 neutropenia (28% v 56% ) but more grade 3 and 4 thrombocytopenia (56% v 13%) than did etoposide-cisplatin. However, there were no thrombocytopenia-related complications in the gemcitabine arm. CONCLUSION: Compared with etoposide-cisplatin, gemcitabine-cisplatin provides a significantly higher response rate and a delay in disease progression without impairing QOL in patients with advanced NSCLC.

PURPOSE: Given the cisplatin-related myelotoxicity and nonhematologic toxicities, we were prompted to undertake a study of the noncisplatin combination of paclitaxel plus gemcitabine to evaluate the efficacy, tolerance, and survival of this combination in patients with locally advanced and metastatic non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients received gemcitabine 2,000 mg/m2 and paclitaxel 150 mg/m2 on days 1 and 15 of a 28-day cycle, for a maximum of eight cycles. RESULTS: Between December 1997 and June 1998, 89 untreated NSCLC patients were enrolled; 30 (34%) had stage IIIB disease (23 with malignant pleural effusion and seven without), and 59 (66%) had stage IV disease. Eighty-six percent of patients had a performance status of 0 or 1. The median number of cycles administered was four (range, one to eight cycles). The mean dose-intensity for both paclitaxel and gemcitabine was nearly 100%. Hematologic and nonhematologic toxicities were mild. Thirty-eight patients received second-line chemotherapy after completion of the study. The overall intent-to-treat response rate was 32.2%, with a higher response rate for stage IIIB patients (43.3%) than for stage IV patients (26.3%). Overall median survival was 9.9 months, and 1-year survival was 38.8% (14.2 months for stage IIIB and 7.7 months for stage IV; P = .007). Median survival was 10.2 months for patients with a performance status of 0 or 1 and 4.8 months for patients with a performance status of 2 (P = .007). CONCLUSION: A biweekly paclitaxel/gemcitabine regimen was well tolerated, with an acceptable response rate and a reasonable median survival time, especially in patients with good performance status. It merits further exploration in future studies.

Single nucleotide polymorphisms (SNPs) in the metabolic pathways of S-adenosylmethionine have been related to global hypomethylation and a lower number of hypermethylated CpG islands of tumor suppressor genes. Hypermethylation of checkpoint and DNA repair genes has been shown to be indicative of chemosensitivity. In the present study, we have examined the SNP of methylenetetrahydrofolate reductase (MTHFR) C677T, which affects DNA methylation patterns and is linked to elevated plasma homocysteine levels in 208 patients with gemcitabine/cisplatin-treated stage IV non–small-cell lung cancer (NSCLC). No differences in response rate were observed according to the MTHFR genotype. However, time to progression was 7.4 months for 68 patients with CC genotype, 5.5 months for 108 patients with heterozygous CT genotype, and 5.2 months for 28 patients with TT genotype. These findings can lead us to distinguish different outcome patterns among patients with stage IV NSCLC whose similar clinical prognostic factors would otherwise indicate similar outcomes. Carriers of the MTHFR 677T allele could benefit from supplementation with folic acid and vitamin B12. The Spanish Lung Cancer Group has undertaken a phase III randomized trial to elucidate this concept.

High-dose epirubicin plus cisplatin was compared with the reference regimen of etoposide/cisplatin in small-cell lung cancer (SCLC). Four hundred two previously untreated patients with SCLC were randomized to receive etoposide 100 mg/m(2) on days 1-3 and cisplatin 100 mg/m(2) on day 1 or epirubicin 100 mg/m(2) and cisplatin 100 mg/m(2) on day 1 every 21 days for a total of 6 cycles. Patients were stratified according to treatment center and extent of disease (limited disease, n = 207; extensive disease, n = 195). Patients with limited disease were treated with thoracic radiation therapy after completion of chemotherapy, and those who exhibited a complete response were advised to receive prophylactic cranial irradiation. The primary endpoint was survival, and secondary endpoints were time to progression (TTP), response, toxicity, and costs. Patient characteristics were generally well balanced in the 2 arms, even though more patients in the epirubicin/cisplatin arm had > 5% weight loss and poor Karnofsky performance index compared with the etoposide/cisplatin arm. One hundred thirty-four patients (66.3%) in the etoposide/cisplatin arm and 126 (63.0%) in the epirubicin/cisplatin arm received all 6 planned cycles of chemotherapy. Response rate, TTP, and survival did not differ significantly between the 2 arms. Grade 3/4 neutropenia and toxic deaths occurred more frequently in the etoposide/cisplatin arm. Epirubicin/cisplatin showed a similar activity with a slightly lower toxicity profile than the reference regimen of etoposide/cisplatin. The epirubicin/cisplatin regimen may be recommended in the treatment of SCLC.

Few types of cancer have had their treatment evolve as rapidly as metastatic renal cell carcinoma (mRCC). Since 2005, six new targeted therapies with proven efficacy have been approved for the treatment of mRCC. The downside is that our knowledge about the mechanisms of action of these therapies and the intrinsic and extrinsic mechanism of resistance has not evolved equally fast, and many questions remain unanswered. The only approved agent to date in the European Union for patients who progress on sunitinib or sorafenib is everolimus. The results of the phase III trial comparing axitinib vs. sorafenib after failure on sunitinib, bevacizumab, temsirolimus, or cytokines have recently been published, and axitinib has recently been licensed by the Food and Drugs Administration. Other phase III trials that are being conducted include a comparison between everolimus plus bevacizumab and everolimus after failure on tyrosine kinase inhibitors, and between temsirolimus and sorafenib after failure on sunitinib. In this article, we will review the available evidence from clinical studies on sequential therapy for mRCC, including those that are still in progress. In addition, information on the mechanism of resistance or tolerance to first-line therapy, recommendations of the main practice guidelines for second-line treatment, potential therapies for third or successive treatment lines, and the major reasons why patients who progress may benefit from a change of mechanism of action will also be discussed.