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J. Bishop

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    E03 - Chemotherapy for NSCLC (ID 3)

    • Event: WCLC 2013
    • Type: Educational Session
    • Track: Medical Oncology
    • Presentations: 4
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      E03.1 - Maximising the Benefit of Chemotherapy for Advanced NSCLC (ID 382)

      14:05 - 14:25  |  Author(s): G. Giaccone

      • Abstract
      • Presentation
      • Slides

      Abstract
      Chemotherapy is still standard treatment for the majority of patients with advanced NSCLC, who do not have specific molecular markers (i.e. EGF mutations, ALK translocations). Platinum based doublets remain standard treatment for most patients and the choice of regimen is based mainly on side effect profile. There is a preference for pemetrexed based therapies for patients with adenocarcinoma histologies, based on one randomized study. Benefit of chemotherapy can be extented by maintenance chemotherapy (pemetrexed), in terms of increased progression-free survival and overall survival. Maintenance with erlotinib has also been approved, although the largest effects are really seen in EGFR mutant patients. Very few chemotherapy doublet regimens have been improved by addition of a third agent, chemotherapy or biological. Bevacizumab was shown to increase response rate, progression-free survival as well as overall survival in one study where carboplatin-paclitaxel was the backbone. Bevacizumab is continued as maintenance. Cetuximab improved survival in addition to cisplatin-vinorelbine, and again cetuximab was continued after the end of chemotherapy. Unfortunately most of the other combinations of biologicals with chemotherapy have been disappointing. Novel agents with different mechanisms of action from the classical tyrosine kinase inhibitors might obtain better results (e.g. PD-1/PD-L1 antibodies). Results of randomzied studies are awaited. The HSP-90 inhibitor gatenespib, in combination with docetaxel gave promising results in a relatively large randomized phase II study, and a phase III study is now underway.

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      E03.2 - Selecting Patients for Maintenance Therapy (ID 383)

      14:25 - 14:45  |  Author(s): L. Paz-Ares

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      E03.3 - Optimal Adjuvant Chemotherapy: Selection of Patients and Agents (ID 384)

      14:45 - 15:05  |  Author(s): K. Kelly

      • Abstract
      • Presentation
      • Slides

      Abstract
      Optimal adjuvant chemotherapy: selection of patients and agents Patients with early stage, resectable non-small cell lung cancer (NSCLC) have the best chance to be cured with 5 year survival rates ranging from 73% for patients with pathological stage IA disease to 24% for patients with pathological stage IIIA disease. However, the presence of micro-metastases will lead to the development of systemic relapse and death in the majority of patients. To improve survival of these patients adjuvant chemotherapy following complete tumor resection has been studied. Three phase III trials with cisplatin-based regimens and the LACE meta-analysis demonstrated increased cure rates by adjuvant chemotherapy and established adjuvant chemotherapy as the standard of care. Randomized Trials The first trial to demonstrate a survival advantage for adjuvant chemotherapy was the International Adjuvant Lung Cancer Trial Cooperative Group (IALT) study. This trial enrolled 1867 patients; 932 patients were randomized to receive chemotherapy (cisplatin plus etoposide, vinorelbine, vinblastine, or vindesine for 3-4 cycles) and 935 patients were randomized to observation. The 5 year overall survival rate significantly favored the chemotherapy arm (Hazard Ratio [HR] 0.86; 95% CI 0.76-0.98; P <0.03). Disease free survival (DFS) was also superior in the treated arm (HR 0.83; 95% CI 0.74-0.94; P=0.003). With longer follow up of 8 years, the HR for overall survival was not significant (HR 91; 95% CI 0.81-1.02; P=0.10) while the HR for DFS retained significance (HR 0.88; 95% CI 0.78-0.98; P=0.02). In 2005, the National Cancer Institute of Canada Cancer Treatment Group (NCIC CTG) reported the results of JBR10. Patients with completely resected stage IB or stage II NSCLC were randomized to receive cisplatin plus vinorelbine (242 patients) or observation (240 patients). An impressive overall survival benefit was observed for the treated group (HR 0.69; 95% CI 0.52-0.91; P=0.04) corresponding to an absolute survival improvement of 15%. In a subgroup analysis, the survival benefit was restricted to patients with Stage II disease. An update of this study, with > 9 years of follow up continued to show a survival benefit for the treated group with an absolute improvement in the 5 year overall survival (OS) rate of 11% (67% versus 56%, respectively) with a HR of .78; 95% CI 0.62-0.99; P=0.04 (11). Subsequently, the results from the ANITA trial (Adjuvant Navelbine International Trialist Association) solidify the role of adjuvant systemic treatment. A total of 840 patients with Stage IB, II, and IIIA NSCLC were randomized to cisplatin plus vinorelbine versus observation. The HR for death was significantly lower for the chemotherapy group (HR= 0.80, 95% CI 0.66-0.96; P=0.017). The 5 and 7 year overall survival was improved by 8.6% and 8.4% in the chemotherapy group, respectively. No benefit was seen in the subset of patients with Stage IB disease (HR 1.10; 95% CI 0.76-1.57; P=NS). To identify which patients might have the greatest benefit from adjuvant chemotherapy, the LACE (Lung Adjuvant Cisplatin Evaluation) meta-analysis was conducted. Individual patient data was collected and pooled from 4,584 patients in 5 trials (BLT, ALPI, IALT, JBR10 and ANITA). The HR of death was 0.89; 95% CI 0.82-0.96; P=0.005, which corresponded to a 5-year absolute survival benefit of 5.4% with chemotherapy. This benefit varied with stage of disease and was not seen for stage IA patients. A positive chemotherapy effect was seen in patients with performance status (PS) 0-1 whereas chemotherapy was potentially harmful for patients with a PS of 2. Other subgroups analyzed including age, sex, histology, type of surgical resection, planned radiation, dose of cisplatin or the second agent used did not affect overall or disease free survival. Elderly patients Since the majority of patients diagnosed with lung cancer are 70 years old or greater, an additional analysis of the LACE data set by age was conducted. Elderly patients (age > 70 years) accounted for 9% of the patients. Their HR of death was better with treatment at .90 (95% CI 0.74-1.16) and was similar to the HR of death for treated patients < 65 years old at .86 (95% CI 0.78-.94). Elderly patients achieved a survival benefit despite having received lower cisplatin doses and fewer number of chemotherapy cycles than their younger counterparts. Tumor size The Cancer and Leukemia Group B (CALGB) trial 9633 evaluated four cycles of adjuvant paclitaxel and carboplatin versus observation in stage IB patients. With mature follow up of 74 months, overall survival was not significantly different between the two groups (HR 0.83; 95% CI 0.64-1.08; P=0.12). No significant improvement in DFS was observed. In an unplanned subgroup analysis based on tumor size a survival advantage for paclitaxel and carboplatin was seen in patients who had tumors >4 cm (HR, 0.69; 95% CI 0.48-0.99; P = .043). In support of this finding, a retrospective analysis of patients with stage IB disease on JBR 10 was conducted according to tumor size of < or > 4 cms. Patients with smaller tumors did not benefit from adjuvant therapy while treated patients with tumors > 4 cm had a favorable 5 year OS rate of 79% compared to 59% for untreated patients (HR .66; 95% CI 0.39-1.14; P=0.13). It is important to remember that in the 7[th] TNM staging system, patients with tumors of > 4 cm could be Stage IB, IIA or IIB. Chemotherapy regimen In the clinical trials described above vinorelbine plus cisplatin was the most commonly used regimen. In a subgroup analysis of LACE, adjuvant cisplatin plus vinorelbine improved survival at 5 years by 8.9% in the vinorelbine cohort and this outcome was superior to the “other” cohort. Today more modern regimens are frequently used based on their activity in advanced disease including cisplatin and gemcitabine, cisplatin and docetaxel and cisplatin and pemetrexed. In summary, adjuvant cisplatin based chemotherapy is the standard of care for patients with resectable Stage II-III NSCLC with a good performance status and should be considered for patients with tumor size > 4 cm. Current strategies to improve outcome of adjuvant chemotherapy focuses on the integration of targeted therapies, tumor vaccines and the identification of prognostic and predictive biomarkers.

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      E03.4 - Lung Cancer in Women (ID 385)

      15:05 - 15:25  |  Author(s): T. Vavala', S. Novello

      • Abstract
      • Presentation
      • Slides

      Abstract
      At the beginning of 20th century only a few hundred cases of lung cancer were diagnosed annually, but the progressive huge spread of tobacco consumption caused a dramatic increase of the incidence of this disease among men and later on among female smokers. US data shows that the prevalence of smoking in American women peaked in 1965 at 33% and remained at that level throughout the 1970s, before beginning to slowly decrease in 1980. In contrast, more than half of American men smoked before 1965, but the prevalence dramatically decreased during the subsequent 20 years. Currently, 18% of American women smoke compared with 23% of men, reflecting the earlier and more marked decline in the prevalence of tobacco use in men. Nowadays, more women in United States die from lung cancer each year than from breast, ovarian and uterine cancer combined: lung cancer is the leading cause of cancer death with more than 110,000 new cases and more than 72,000 estimated deaths in 2013. In European countries there are more than 79,000 new cases of lung cancer in female sex per year and 82,000 is the estimated death number in 2013, that means 9,024 more than what was reported in 2009. Approximately 80% - 85% of lung cancers in women are caused by cigarette smoking. Wang et al. investigated the association of both active and passive smoking on lung cancer risk in a prospective cohort of more than 90,000 post-menopausal women: the results of the Women’s Health Initiative Observational Study (WHI-OS) have been presented at 2013 ASCO annual meeting and evidenced an higher lung cancer incidence, particularly small cell lung cancers and squamous lung cancers, in current smokers (Hazard Ratio, HR 13.44, 95%, CI 10.80-16.75) and former smokers (HR 4.20, 95% CI 3.48-5.08) compared to never smokers. In the same study, among never smoking women, passive exposure, as an adult at home for > 30 years, was associated with a trend of increased risk (HR 1.61, 95% CI 1.00-2.58) for lung cancer, confirming findings of previous prospective cohort studies. In recent times, an increased proportion of non-smoking female patients, with earlier age at diagnosis and a majority of adenocarcinoma has been observed, particularly in Asian countries. Prevalence of lung cancer in females without history of tobacco smoking is estimated to represent 19% compared with 9% of male lung carcinoma in the United States. Freedman et al. reported, on a cohort of nearly 500,000 individuals, aged from 50 to 71 years, a significant increase in the rate of lung cancer for women who did not smoke, compared with male non-smokers, whereas no increased risk was described in current and former female smokers compared with matched males. Hormonal status is one of the potential explanations for gender differences. Estrogens are involved in lung tumorigenesis and progesterone receptor expression has been described in non small cell lung cancers (NSCLC). Combination of estrogen and progesterone works synergistically in vitro to promote vascular endothelial growth factor secretion increasing tumor-associated angiogenesis. Chlebowski et al. examined estrogen plus progestin (E+P) association with lung cancer incidence and outcome evaluating more than 30,000 postmenopausal women. Results have been presented at 2013 ASCO annual meeting: in non users of E+P, lung cancer incidence and deaths from lung cancer were significantly and substantially greater in current smokers versus never smokers (p< 0.0001 for both comparisons). In current smokers, lung cancer incidence and deaths from lung cancer were significantly and substantially greater in E+P users versus non-users (p=0.0021 and 0.0005, respectively), nearly doubling a smoker’s already high risk of death from lung cancer. Conversely, the role of androgens remains unclear. Harlos et al. evaluated more than 3,000 men with lung cancer evidencing that exposure to androgen deprivation therapy (ADT) is associated with significantly better survival when compared with no exposure. Patients exposed to ADT after their diagnosis were found to have a significantly better survival than those not exposed (HR 0.36 p=0.0007). This effect was also seen in those who received ADT before and after diagnosis (HR 0.53 p<0.0001). With regard to specific gene alterations there are relevant differences in men and women. The most widely recognized is the epidermal growth factor receptor (EGFR) mutation, that is found at a much higher frequency in adenocarcinomas, women, Asians and never smokers. Mutations in HER2 gene, although much rarer, target the same subpopulations. Mutations in EGFR (and HER2) are mutually exclusive of K-ras mutations: these are primarily observed in smokers and historically associated with male sex, but there are also publications demonstrating an higher frequency in women of “non-classical” type of K-ras mutations even if these data need further validations. The echinoderm microtubule associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation has been evidenced to occur more frequently in young patients, light or never smokers, while no major differences have been clearly stated between genders. B-Raf (V600) is described in 2% of patients with lung adenocarcinoma in western countries, related with worse prognosis and it is noted more frequently in women. An analysis of the p53 mutation databases indicated that the different spectra of p53 mutational patterns among smoker and never smoker cancers were almost entirely a result of differences between lung cancers in women, whereas male tumours did not show significant differences. Finally, recent studies investigated the role of telomere shortening in lung cancer. Kim et al. hypothesized that relative telomere length may be associated with recurrence in early stage NSCLC after curative resection. Longer telomeres were significantly associated with higher risk of developing recurrence in female (HR 2.25; 95% CI, 1.02-4.96, P= 0.044) and adenocarcinoma subgroups (HR 2.19; 95% CI, 1.05-4.55). All these findings provide multiple evidence for the specificities of lung cancer in women. The different expression of specific biomarkers, which could be targeted by therapy, will improve research towards personalized sex-based investigations, stimulating the development of further gender-based approaches in thoracic oncology.

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    O27 - Clinical Trials and Practice (ID 142)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Other Topics
    • Presentations: 8
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      O27.01 - Thromboembolism in lung cancer - an area of urgent unmet need (ID 2096)

      16:15 - 16:25  |  Author(s): M. Alexander, S.W. Kirsa, R. Wolfe, M. Macmanus, D. Ball, B. Solomon, K. Burbury

      • Abstract
      • Presentation
      • Slides

      Background
      Current management of lung cancer (LC) (chemotherapy - CHT, radiotherapy – RT, and biological therapies) occurs predominantly in the ambulatory care (AC) setting. Post-surgery hospital admission is becoming progressively shorter due to advances in technique and greater reliance on home recovery.[1,2]As such, LC management occurs outside the scope of current thromboprophylaxis (TP) guidelines.[2-8] Recommendations for TP strategies in these high thromboembolism (TE) risk patients are lacking.[9] The aim of this study was to profile TE incidence in LC patients receiving anti-cancer therapy, exploring patient-, disease- and treatment-related risk factors associated with higher thrombotic rates. This could identify high-risk populations, disease features and/or treatment periods that warrant strong recommendations for targeted preventative strategies to reduce LC-associated TE, and in particular consideration of pharmacological-TP (P-TP).

      Methods
      Retrospective review of LC patients referred to Peter MacCallum Cancer Centre, a tertiary dedicated cancer centre, between 01/07/11 - 30/06/12 for anti-cancer therapy. Data were collected from medical, pharmacy, pathology and diagnostic imaging electronic records. Follow up was defined as time from study entry (referral date) to first occurring event; TE, death, loss to follow-up or study end. Hazard ratios were calculated using Cox proportional hazards model.

      Results
      222 patients were followed for a median 10 months from time of first hospital registration. The cohort was predominantly newly diagnosed (77%), with advanced disease (71%), NSCLC (92%). Among NSCLC adenocarcinoma was the predominant histological subtype (77%). 30% of patients received multiple lines of therapy within the study period; 49% received CHT (alone or combination chemoradiotherapy, CRT), 73% RT (alone or CRT), 19% biologic therapy and 19% surgical intervention. 10.8% of patients had radiologically confirmed TE, giving an incidence rate of 131 events per 1000 person-years (95%CI 87-195). 83% (20/24) of events occurred in the AC setting; 71% symptomatic, 29% asymptomatic. 16 events were pulmonary embolism (PE) (5 fatal), 4 deep vein thrombosis (DVT), 1 combination DVT/PE, 1 atrial and 2 arterial thrombosis. TE occurred frequently in both NSCLC and SCLC (10.8% and 10.5% respectively), and more frequently among patients with adenocarcinoma compared to squamous cell histology (14.7% and 5.3% respectively). Presence of more advanced or metastatic disease, prior history of TE and comorbidity score>2 were associated with higher rates of TE. More than a third (38%) of TE events occurred during the CHT period, 13% post-surgery, 8% during RT and biologic therapy respectively. CHT demonstrated more than five-fold increased TE risk compared to no CHT (HR 5.7 95% CI 2.2-14.8) with a similar finding for RT (HR 5.2 95%CI 2.0-13.2). Importantly, P-TP was not routinely or systematically prescribed for ambulant LC patients during any treatment phase, at this institution.

      Conclusion
      LC patients are at high risk of preventable and potentially life-threatening thrombotic events. TE events occur frequently in the AC setting and consideration of P-TP is warranted, but not used routinely due to a lack of high quality data. There is a demand for appropriate risk-stratification and directed preventative strategies. Prospective data and the development of dynamic risk profiles which can direct clinical practice are needed.

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      O27.02 - Preliminary results from the FRAGMATIC trial: A randomised Phase III clinical trial investigating the effect of FRAGMin® Added to standard Therapy In patients with lung Cancer. (ID 1799)

      16:25 - 16:35  |  Author(s): F. Macbeth, S. Noble, G. Griffiths, R. Chowdhury, C. Rolfe, K. Hood, S. Linnane, B. Moore, D. Cohen, R. Cowles, M. Longo, D. Knoyle

      • Abstract
      • Presentation
      • Slides

      Background
      Venous thromboembolism (VTE) is common in lung cancer patients and the incidence is increased by treatments including radiotherapy, surgery and chemotherapy. Research suggests a survival benefit in cancer patients receiving long term low moecular weight heparin (LMWH). LMWH may also have antimetastatic effects through the inhibition of P-selectin. This trial was developed to investigate whether or not adding LMWH to standard treatment increases overall survival. The study is funded by a research grant from Cancer Research UK (C13275/A5323) and free drug and an educational grant from Pfizer. The trial is sponsored by Velindre NHS Trust, and coordinated by the Wales Cancer Trials Unit, Cardiff, UK.

      Methods
      An open label, multi-centre, Phase III randomised controlled trial in patients with lung cancer comparing anticancer treatment according to local practice plus dalteparin (Fragmin®), with anticancer treatment alone. Eligible patients had a histopathological or cytological diagnosis of primary bronchial carcinoma (SCLC or NSCLC) within the previous 7 weeks, performance status 0, 1, 2 or 3 and were willing and able to inject daily subcutaneous injection. The dalteparin was given as a daily 5,000 IU subcutaneous injection for 24 weeks. The primary outcome measure is overall survival and the secondary outcome measures include toxicity, VTE-free survival, metastasis-free survival, quality of life, and cost utility. To detect an advantage of 5% in overall survival at 1 year (to 30%) a total of 2200 patients were required (1100 in each arm).

      Results
      2202 patients were enrolled and randomised in 4 years. The two groups were well balanced for key variables. 60% were men; the median age was 65 years; 82% had NSCLC (5% Stages I and II, 38% Stage III, 57% Stage IV) and 18% SCLC (63% Extensive Disease); 85% had WHO PS 0 or 1; 95% received chemotherapy as first treatment. 56% of those in the dalteparin arm received at least 90 of the 168 planned injections. By 1/8/2013 there had been 1891 deaths recorded and, on advice from the Independent Data Monitoring Committee, the primary results have been released. There was no significant difference in overall survival (HR 0.97; 95% CI 0.89-1.06) nor in metastasis-free survival. Exploratory subgroup analyses do not suggest a significant survival advantage in any subgroup. Dalteparin use was not associated with a significant increase in major bleeding complications. There were 78 (7.1%) confirmed VTEs in the control group and 47 (4.1%) in the treatment group.

      Conclusion
      This large RCT which recruited mainly good PS lung cancer patients having chemotherapy, has confirmed that prophylactic dalteparin reduces the risk of VTE events without a significant increase in major bleeding. The baseline VTE risk of 7% and relative risk reduction of 40% are consistent with previous studies. There was no significant difference in overall survival. These results do not support a policy of routine prophylactic anticoagulation of all lung cancer patients undergoing chemotherapy.

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      O27.03 - Meta-analysis of progression-free survival and objective response rate as predictors of overall survival in locally advanced or metastatic non-small-cell lung cancer (ID 3170)

      16:35 - 16:45  |  Author(s): E.J. Turner, P. McCloud, P. Germanos, F. Dehle, S. Norris, J. Tan, P.L. Mitchell

      • Abstract
      • Presentation
      • Slides

      Background
      Improving overall survival (OS) in locally advanced or metastatic non-small-cell lung cancer (NSCLC) remains a goal for clinicians. OS is often the primary endpoint in Phase III clinical trials, however with the increased use of multiple lines of treatment and crossover/rescue therapy in NSCLC trials, overall survival differences are frequently confounded. Other clinically meaningful endpoints such as progression-free survival (PFS) are becoming increasingly important. A systematic review and meta-analysis was undertaken to investigate whether the treatment effect on PFS, or objective response rate (ORR), was predictive of the treatment effect on OS in locally advanced or metastatic NSCLC.

      Methods
      Embase, MEDLINE and the Cochrane Library databases were searched to identify relevant published randomised controlled trials (RCTs). Included RCTs compared pharmacological treatments in two or more groups in patients with locally advanced or metastatic (Stage IIIb or IV) NSCLC. The reported outcomes had to include median PFS and median OS. Data were analyzed with locally weighted least squares regression (LOWESS) to validate the linear relationship. Unweighted linear regression and weighted linear regression were used to estimate the relationship between OS treatment difference and PFS treatment difference. A similar analysis was also done to compare ORR difference and OS difference. The analysis also considered whether potential baseline prognostic factors could also change OS difference. Univariate weighted linear regression was used to assess the relationship of each prognostic factor with OS difference, followed by multivariate weighted linear regression.

      Results
      A total of 124 RCTs (N=40,568 patients) were included in the analysis. Of the 124 trials, 98 (79%) were published since 2005. The age of patients ranged from middle aged cohorts to the elderly. There were 87 studies (70%) with first-line therapy and therapy type was predominantly chemotherapy (71 studies, 57%). The LOWESS of OS difference versus PFS difference was a relatively straight line, therefore a linear relationship appeared to be justified. Weighted linear regression showed a highly significant relationship between OS treatment difference and PFS treatment difference [slope 1.317 months (95%CI 1.000, 1.634) p<0.001 R[2] = 36.6%]. Diagnostic plots revealed several statistical outliers. A weighted linear regression of OS difference versus PFS difference with six outlier studies removed also showed a highly significant linear relationship [slope 0.994 months (95%CI 0.749, 1.240) p<0.001 R[2] = 36.7%]. The relationship between ORR difference and OS difference was also significant [slope 12.503 (95%CI 7.042, 17.963) p<0.001 R[2] = 16.0%]. Univariate weighted linear regressions showed that the only baseline prognostic factor with a significant linear relationship with OS difference was the proportion of patients with non-squamous histology. Multivariate weighted linear regression showed none of the baseline prognostic factors was significant when PFS difference or ORR difference was included in the model.

      Conclusion
      The treatment effect on PFS was predictive of the treatment effect on OS. For a 1 month increase in PFS treatment difference, OS treatment difference increases by approximately 1.3 months. A 10% increase in ORR treatment difference was also associated with an increase in OS of 1.25 months. PFS is an important outcome for healthcare decision-making.

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      O27.04 - DISCUSSANT (ID 4014)

      16:45 - 17:00  |  Author(s): G. Richardson

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      O27.05 - Is primary tumor standardized uptake value (SUV) an independent prognostic factor for non-small cell lung cancer (NSCLC)? A meta-analysis based on individual patients data. (ID 3888)

      17:00 - 17:10  |  Author(s): M. Paesmans, C..O. Wong, E. Patz, R. Komaki, S. Eschmann, R. Govindan, J. Vansteenkiste, A. Meert, W.K. De Jong, N.K. Altorki, K. Higashi, A. Van Baardwijk, G. Borst, L. Ameye, J. Lafitte, T. Berghmans, C. Hossein-Foucher, A. Scherpereel, C. Garcia, P. Flamen, R. Rami-Porta, J. Sculier

      • Abstract
      • Presentation
      • Slides

      Background
      [18]F-fluoro-2-deoxy-D-glucose positron emission tomography complements conventional imaging for staging lung cancer although its ability to predict outcome is less well established. Two literature-based meta-analyses suggest a prognostic value in univariate analysis. To assess FDG-PET value in predicting survival adjusted for some known prognostic factors, we carried out a meta-analysis based on individual patients data from multiple independent studies.

      Methods
      Following literature search, and after writing of a protocol for the meta-analysis, we contacted the authors of identified studies and requested individual patients data; we also tried to collect some unpublished data. Data analysis used Cox regression models stratified for the study with overall survival as primary outcome. SUV max was used as a binary covariate (median value for each study).

      Results
      Data were collected for 1526 patients (57% of the identified patients) from 11 publications and 1 unpublished series (median age : 64 years, 60% male patients, squamous cell in 34%, adenocarcinoma in 47%, stages I-II in 58%). Combined univariate hazard ratio (HR) was 1.43 (95% CI : 1.22-1.66); no statistically significant interaction between SUV and one of six additional freatures (age, gender, histology,stage, tumors size –in stages I-III patients- and surgical treatment), was found except for stage (p=0.05) with a decreased prognostic value of SUV for stage IV patients. Without considering SUV, multivariate analysis identified, in stage I-III patients, age, stage, tumor size and surgical treatment as independent prognostic factors. The addition of SUV improved that model : HR estimate for SUV effect was 1.58, statistically significant (95% CI : 1.27-1.96), p<0.0001. No interaction was found with SUV. When tumor size was not included in the tested covariates, we found SUV of additional value (adjustment for age, stage, surgical treatment) with a HR of 1.35 (95% CI : 1.15-158). Interaction between SUV and stage was detected, restricting the significant impact of SUV on survival to stage I-III patients.

      Conclusion
      Conclusions : Although suffering from selection bias and lack of homogeneous SUV assessment, these data suggest that SUV at the time of diagnosis is an independent prognostic marker for patients with stage I-III NSCLC. The utility of SUV in predicting survival in stage IV patients requires further studies.

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      O27.06 - Resistance training in patients with radically treated respiratory cancer: mature results of a multi-centre randomised phase 3 trial (REINFORCE) (ID 678)

      17:10 - 17:20  |  Author(s): J.P. Van Meerbeeck, B. Salhi, C. Haenebalcke, S. Perez-Bogerd, M.D. Nguyen, T.L.A. Malfait, K.Y. Vermaelen, V.F. Surmont, G. Van Maele, R. Colman, E. Derom

      • Abstract
      • Presentation
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      Background
      There is a lack of data on the effect of conventional resistance training (CRT) on exercise capacity, muscle strenght and quality of life (QoL) in patients with lung cancer. Whole body vibration (WBV) is proposed as an alternative to CRT. We investigated the effect of a radical treatment and of two post-treatment resistance training programmes on the 6-minutes walking distance (6MWD).

      Methods
      Selected patients with clinical stage I-IIIB (non-) small cell lung cancer or I-II mesothelioma were evaluated before (M1) and at completion (M2) of their radical treatment, and thereafter randomised to either control (CON), CRT or WBV. 6MWD was measured at M1, M2 and at least 12 weeks (w) after randomisation (M3) considering a minimal clinically important difference (MCID) of 54 m. Assuming that this MCID would occur in 10% of the CON-group and aiming for an increase to at least 50% in the combined intervention groups (CRT and WBV), a sample size of 25 participants in each arm was required for a power of 90%. Secondary endpoints were estimated by appropriate MCID's for maximal exercise capacity (Wmax), muscle strenght (Quadriceps Force (QF)) and QoL (physical functioning (PF), fatigue (F), pain (P) and dyspnea D)). Multiple imputation was used to correct for patients not finishing the intervention.

      Results
      Of the 86 patients completing radical treatment, 70 were randomised: 24 to CON, 24 to CRT and 22 to WBV. Characteristics at M1 were well balanced. Radical treatment significantly decreased 6MWD, Wmax, QF, PF and increased P, F and D at M2. At M3, 20 of 37 (54%) patients in the combined CRT-WBV-group reached the MCID for 6MWD vs. 5 of 21 CON (24%) patients (p=0·031). 6MWD increased with 95 m (58–132) in CRT (p<0·0001), 37 m (-1–76) in WBV (p=0·06) and 1 m (-33–36) in CON (CRT vs. CON p=0·0006 and WBV vs. CON p=0·16). CRT and WBV patients recovered and exceeded their M16MWD, albeit not significantly. A significant mean increase in Wmax occurred in both CRT and WBV but not in CON, while QF increased only significantly in CRT. The mean score for PF at M3 improved in CON and WBV but only significantly with WBV. The mean score for P and F at M3 did not change significantly, however the MCID for F was reached in 37% of CRT, 44% of WBV and 30% of CON-patients. The mean score for D at M3 decreased significantly after WBV only. Multivariate analysis showed that there was no significant interaction between rehabilitation and surgery with regard to the MCID in 6MWD (p=0.96).

      Conclusion
      Radical treatment significantly impairs exercise capacity, muscle strength and QoL. CRT significantly improves and restores functional exercise capacity, whilst WBV does not fully substitute for CRT. Resistance training by CRT should be offered to radically treated lung cancer and mesothelioma patients. Supported by research grant 070708 of the Belgian Government Agency of Innovation by Science and Technology for applied Biomedical Research (NCT: 00752700)

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      O27.07 - Molecular multidisciplinary tumor board (MMTB) for lung cancer patients: 2-year experience report (ID 2865)

      17:20 - 17:30  |  Author(s): B. Besse, L. Lacroix, L. Faivre, V. Kahn-Charpy, M. Ngo Camus, N. Auger, V. Koubi-Pick, J. Adam, V. Thomas De Montpreville, P. Dorfmuller, C. Le Pechoux, M. Macerelli, T. Le Chevalier, J. Soria, B. Lacas, J. Pignon, A. Rahal, V. Polo, D. Planchard

      • Abstract
      • Presentation
      • Slides

      Background
      Molecular analysis (MoA) of non-small cell lung cancer has led to definition of many subgroups that require dedicated treatments, strategy and trials. We created a monthly MMTB dedicated to lung cancer patients (pts) with potential driving molecular abnormalitie(s). MMTB includes physicians from the lung tumor board and the phase I unit, pathologists and biologists. A medical report summarizes the findings and treatment recommendations. We report 2 years of activity of MMTB.

      Methods
      All consecutive files discussed in MMTB in Gustave Roussy were reviewed. Tumor and pts characteristics were collected as well as treatment. Pts outcome was calculated from the MMTB.

      Results
      245 pt files were discussed between February 2010 and March 2012. 53% were male, 27% never-smokers, 89% had PS 0 or 1, median age was 59. Clinical initial stage was III-IV in 17 pts (7%) and 78%/11%/11% were adenocarcinoma/squamous cell carcinomas/others NSCLC. Time from diagnosis to MMTB was 7 months (m) (1-222), 102 (42%) of pts received more than 1 line of treatment before MMTB. Biopsy for MoA mostly came from CT guided biopsies (61%), surgery (22%) or endoscopy (15%). Biopsy was repeated in 20% of pts to get enough material for MoA. The MoA results were ALK rearrangement in 10%, exon 18/19/21 EGFR mutation (mut) in 2/14/8%, KRAS mut in 30%, PI3KCA mut in 0.4%, BRAF mut in 3%, HER2 mut in 1%, FGFR1 amplification in 3%, other rare mutations in 14%. MMTB recommendations were: a clinical trial in 75 pts (31%), receive an EMA-approved drug in 49 pts (20%), an off-label commercial drug in 18 pts (7%), an expanded access program in 18 pts (7%), none in 85 pts (35%). Out of the 160 MMTB pts with treatment recommendations, 63 (42%) received the proposed targeted therapy and 16 (11%) might receive it at the time of disease progression. After MMTB, 84 pts (34%) received 1 line, 66 pts (27%) 2 lines or more, 56 pts (23%) no treatment (unknown in 39 pts). Median follow-up is 20.6 m. Progression-free (in 224 pts) and overall survivals (OS, in 221 pts) from MMTB are 3.5 and 13.4 m. In univariate analysis for OS, the pts who received the recommended treatment from the MMTB had a better prognosis (hazard ratio [HR]: 0.56, p=0.002), confirmed in multivariate analysis (HR=0.61 [95% confidence interval: 0.42-0.88], p=0.009) after taking into account histology, previous platinum-based treatment and the number of previous treatment lines.

      Conclusion
      MMTB leads to treatment recommendations in a majority of the pts, fosters inclusion in clinical trials or expanded access programs, and limits the use of off labelled drugs. Updated data will be presented

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      O27.08 - DISCUSSANT (ID 4015)

      17:30 - 17:45  |  Author(s): A.Y. Chang

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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