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M. Lind
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MO09 - Mesothelioma I (ID 120)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track:
- Presentations: 1
- Moderators:K. Suzuki, S.G. Armato III
- Coordinates: 10/28/2013, 16:15 - 17:45, Bayside 204 A+B, Level 2
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MO09.02 - A Randomised Phase II trial of Pegylated Arginine Deiminase in patients with Malignant Pleural Mesothelioma (ID 1355)
16:20 - 16:25 | Author(s): M. Lind
- Abstract
- Presentation
Background
Preclinically, arginine deprivation has shown activity as a novel antimetabolite strategy for MPM patients who are deficient for the rate-limiting enzyme in arginine biosynthesis argininosuccinate synthetase (ASS1). Here, we examine the efficacy and safety of the arginine-lowering agent ADI-PEG20 (Polaris Group, San Diego, US) among patients with MPM.Methods
We performed a multicentre randomised phase II clinical trial, based on patients with good performance status (0 or 1), non-resectable disease, ASS1-deficient MPM, and measurable disease. Patients were randomized 1:2 to receive best supportive care (BSC) or BSC+ADI-PEG20, stratified by: gender, histology (sarcomatoid versus non-sarcomatoid), prior treatment (chemonaive or previous platinum combination therapy), and centre. The primary endpoint, progression-free survival (PFS), is assessed by modified RECIST, and secondary endpoints include overall survival, tumor response rate, and toxicity. Translational endpoints included measurement of plasma arginine, citrulline and ADI-PEG20 antibody levels, assessment of metabolic response by [18F]Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and ASS1 methylation status using Illumina’s 450K DNA methylation array. The target sample size was estimated to detect a PFS hazard ratio of 0.60. [Trial funded by Cancer Research UK].Results
ASS1 deficiency was detected in 98 of 214 patients (46%) of which 68 were randomized on the trial (44 ADI-PEG20+BSC and 24 BSC alone). 66 patients have progressed so far (42 ADI-PEG20+BSC vs. 24 BSC alone), and 32 patients were alive (23 ADI-PEG20+BSC vs. 9 BSC alone). The hazard ratio for PFS was 0.53 (95%, CI 0.31 to 0.90, p=0.02) with a median PFS of 98 days for patients randomized to ADI-PEG20+BSC compared with 59 days for patients receiving BSC alone. ADI-PEG20 toxicity in patients with MPM has been consistent with previous trials of ADI-PEG20 in melanoma and liver cancer: commonly skin injection site reactions (grade 1-2), infrequent episodes of neutropenia (range: grade 1-4), anaphylactoid reactions (2 patients with grade 3 episodes) and serum sickness (1 patient). The best response by modified RECIST was stable disease. Metabolic responses (in 39 evaluable ADI-treated patients) were as follows: 46% with partial response (18/39), 31% with stable disease (12/39), 15% progressive metabolic disease (6/39) and 8% mixed metabolic response (3/39) by FDG-PET assessment. There was a significant difference between IHC assessed ASS1-negative and ASS1-positive patients and the methylation status of the ASS1 gene (p=0.025).Conclusion
ADI-PEG20 is generally well tolerated and shows evidence of clinically significant activity in patients selected for arginine-dependent MPM demonstrating differential methylation of ASS1. Arginine deprivation may have a role in the future management of MPM either alone or in combination with selected therapies.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO13 - SCLC I (ID 118)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:C.K. Liam, E.S. Santos
- Coordinates: 10/29/2013, 10:30 - 12:00, Bayside 201 - 203, Level 2
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MO13.07 - Survival of small cell lung cancer patients undergoing lung resection in England 1998-2009 (ID 1691)
11:10 - 11:15 | Author(s): M. Lind
- Abstract
- Presentation
Background
Chemotherapy or chemoradiotherapy is the recommended treatment for small cell lung cancer (SCLC) except in stage I disease where clinical guidelines state there may be a role for surgery based on favourable outcomes in case series. Evidence supporting adjuvant chemotherapy in resected small cell lung cancer is limited but this is widely offered.Methods
Data on 359,873 patients who were diagnosed with a first primary lung cancer in England between 1998 and 2009 were grouped according to histology (SCLC; non-SCLC [NSCLC]) and whether they underwent a surgical resection. We explored their survival using Kaplan-Meier analysis and Cox regression, adjusting for age, sex, comorbidity and socio-economic status.Results
The survival of 465 resected SCLC patients was lower than resected NSCLC patients (five-year survival 31% and 45%, respectively), but much higher than patients of either group who were not resected (3%). The difference between resected SCLC and NSCLC diminished with time after surgery. Survival was superior for the subgroup of 198 “elective” SCLC where the diagnosis was most likely known before resection than for the subgroup of 267 “incidental” cases, where the SCLC diagnosis was likely to have been made after resection.Conclusion
These data serve as a natural experiment testing the survival after surgical management of SCLC according to NSCLC principles. SCLC patients treated surgically for early stage disease may have survival outcomes that approach those of NSCLC, supporting the emerging clinical practice of offering surgical resection to selected SCLC patients.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO22 - Advanced Disease and Outcomes (ID 103)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Surgery
- Presentations: 1
- Moderators:T. Yano, J. Roth
- Coordinates: 10/30/2013, 10:30 - 12:00, Parkside 110 A+B, Level 1
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MO22.01 - High procedure volume is strongly associated with improved survival after lung cancer surgery (ID 1704)
10:30 - 10:35 | Author(s): M. Lind
- Abstract
- Presentation
Background
Surgical resection is the first line treatment offered to patients with early stage non-small cell lung cancer (NSCLC) who are considered medically fit. Many studies have shown that patients undergoing surgery for lung cancer benefit from receiving treatment in hospitals where high numbers of lung cancer resections are carried out. This study explores the association between hospital volume and survival among all NSCLC patients diagnosed in England who underwent surgical resection and takes into account the differences in case selection and propensity to resect.Methods
We analysed data on 134,293 patients with NSCLC diagnosed in England between 2004 and 2008 of whom 12,862 (9·6%) underwent surgical resection. Hospital volume was defined according to the number of patients with resected lung cancer in each hospital in each year of diagnosis. Cox proportional hazard regression analyses were used to assess the association between hospital volume and survival among resected patients. We calculated multivariable hazard ratios according to hospital volume, with adjustment for potential confounders (sex, age, socioeconomic deprivation, comorbidity and resection quintile). In addition, to account for the risk of death potentially varying between groups of patients treated within a given hospital, a shared frailty Cox model was used, with hospital as a random effect. The follow-up period was divided into three pre-defined periods: 0-30 days, 31-365 days and >365 days post-surgery.Results
There was increased survival in hospitals performing more than 150 surgical resections compared with those carrying out less than 70 [HR 0·78 (95% CI 0·67-0·90), p~trend~ <0·01]. The association between hospital volume and survival was present in all three periods of follow-up, but the magnitude of the association was greatest in the period 0-30 days (HR for the 150+ hospital volume group compared with less than 70: 0·58, 95% CI 0·38-0·89) and smallest in the period after 365 days (HR 0·84, 95% CI 0·71-0·99).Conclusion
High volume hospitals have higher resection rates, operate on patients who are older, have lower socioeconomic status, more comorbidities and despite that they achieve better survival, most notably in the early post-operative period.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
