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A. Masood
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P1.05 - Poster Session with Presenters Present (ID 457)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.05-047 - Early Mortality in Patients with Non-Small Cell Lung Cancer Undergoing Adjuvant Chemotherapy (ID 5523)
14:30 - 14:30 | Author(s): A. Masood
- Abstract
Background:
Although adjuvant chemotherapy improves survival in patients with completely resected non-small-cell lung cancer (NSCLC) compared to surgery alone, it is also associated with potentially disabling or lethal adverse events. Since there is limited information on the early mortality among patients undergoing adjuvant chemotherapy, we used the National Cancer Data Base (NCDB) to calculate the percentage of deaths within the first 6 months from starting chemotherapy.
Methods:
The NCDB was queried for patients aged 18 or older, diagnosed with stage IB to IIIA NSCLC (AJCC 7[th] edition) from 2004 to 2012, who underwent surgery with negative margins followed by multi-agent chemotherapy, starting within 120 days from the surgical resection. Patients who received radiation therapy were excluded. Age groups were divided into <50, 51-60, 61-70, 71-80 and >80 years. Early mortality from months 1 to 6 were calculated and multivariate logistic regression was performed to identify clinical variables independently associated with mortality at six months from the date of initiation of adjuvant chemotherapy.
Results:
A total of 19,791 patients met the eligibility criteria. The median age was 65 (range 19-89). The percentage of deaths at 1, 2, 3, 4, 5 and 6 months were 0.6%, 1.3%, 1.9%, 2.6%, 3.3% and 4.2% respectively. The percentages of death at 6 months for each age group from < 50 years to > 80 years were 2.7%, 3.2%, 4.1%, 5.3% and 7.8% respectively. Factors independently associated with increased 6-month mortality included increased age, male gender, higher Charlson-Deyo co-morbidity score (CDCS), type of surgery, length of stay (LoS) > 6 days and 30-day readmission (Table).
Conclusion:
There is a high risk for early mortality among patients undergoing adjuvant chemotherapy for NSCLC, particularly in patients older than 70, with high co-morbidity score and a more complicated post-operative period.Table. Multivariable analysis
Variable OR (95% CI) P-value Age ≤ 50 Reference Reference 51-60 1.08 (0.74-1.60) 0.68 61-70 1.33 (0.91-1.95) 0.15 71-80 1.59 (1.06-2.38) 0.03 > 80 2.27 (1.29-3.98) 0.004 Gender Male Reference Reference Female 0.70 (0.59-0.82) < 0.001 CDCS 0 Reference Reference 1 1.13 (0.95-1.34) 0.15 2 1.58 (1.26-1.98) < 0.001 Surgery Sub-lobar Reference Reference Lobectomy 0.72 (0.53-0.97) 0.03 Pneumonectomy 0.97 (0.68-1.39) 0.87 Stage IB Reference Reference II 1.29 (1.04-1.59) 0.02 IIIA 2.28 (1.81-2.87) < 0.001 LoS ≤ 6 days Reference Reference > 6 days 1.24 (1.06-1.46) 0.008 30-day readmission No Reference Reference Yes 1.54 (1.20-1.99) 0.001
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P1.07 - Poster Session with Presenters Present (ID 459)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.07-035 - Circulating Cell-Free Tumor DNA (cfDNA) Testing in Small Cell Lung Cancer (ID 6193)
14:30 - 14:30 | Author(s): A. Masood
- Abstract
Background:
The diagnosis of small cell lung cancer (SCLC) is often made using fine needle aspiration or small biopsy of tumor specimens that are typically insufficient for next generation sequencing (NGS) analysis. Guardant360 (G360), a blood-based liquid biopsy that analyzes circulating free tumor DNA, may allow the detection of potentially targetable gene abnormalities without the need for repeated tissue biopsies.
Methods:
Peripheral blood samples from patients with SCLC were collected in two 10 mL tubes. Cell-free DNA was extracted and analyzed by digital sequencing for the detection of single nucleotide variants (SNVs), small Insertions and Deletions (INDELs), Copy Number Alterations (CNAs), and gene fusions. The Tumor Alterations Relevant for Genomics-Driven Therapy (TARGET) curated database (http://www.broadinstitute.org/cancer/cga/target) was queried for potentially actionable alterations.
Results:
240 samples from 227 de-identified patients were collected between June 2014 and June 2016. 7 patients had more than one sample analyzed. During this time period, the number of genes in the panel increased from 54 (10 samples) to 68 (87 samples) and finally to 70 (143 samples). The median time from sample collection to reporting was 13 days (range 8-28 days). Alterations in at least one gene were found in 222 (92.5%) of samples and 210 (92.5%) patients. SNVs in TP53 and RB1 were seen in 72.4% (152/210) and 25.7% (35/136) of patients with detectable alterations respectively. The most common potentially actionable alterations were amplifications of FGFR1 (11.8%) and ERBB2 (7.1%). MYC amplification, which was not considered an actionable alteration by TARGET but has been associated with sensitivity to Aurora kinase inhibitors in pre-clinical studies, was observed in 15.8% of patients. Eight patients had EGFR activating mutations (exon 21 L858R mutation or exon 19 deletion), of which 2 patients also had EGFR T790M mutation, likely representing transformation from NSCLC following targeted therapy with EGFR Tyrosine kinase inhibitors. KIF5B-ALK and AFAP1-RET fusions were seen in 1 patient each.
Conclusion:
G360 is a rapid non-invasive NGS platform which may be particularly useful in patients with advanced stage SCLC where tissue samples may be suboptimal for NGS. Due to the limited treatment options in this patient population, the detection of potentially actionable genes through G360 may provide valuable information to guide treatment decisions.
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P2.06 - Poster Session with Presenters Present (ID 467)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.06-017 - Amethyst NSCLC Trial: Phase 2 Study of MGCD265 in Patients with Advanced or Metastatic NSCLC with Activating Genetic Alterations in MET (ID 5384)
14:30 - 14:30 | Author(s): A. Masood
- Abstract
Background:
MGCD265 is a potent, orally available, small molecule RTK inhibitor of MET and Axl, both of which mediate signals for cell growth, survival, and migration. The Amethyst NSCLC trial is designed to evaluate the activity of MGCD265 in patients with NSCLC exhibiting genetic alterations involving MET. Alterations in MET, including gene amplification and/or genetic mutations, occur in approximately 7% of NSCLC cases converting MET to an oncogene capable of driving cancer development and progression. Amplification of MET has been associated with a poor prognosis in NSCLC. In addition, various genetic mutations result in the deletion of exon 14 in MET mRNA (METex14del) and the subsequent loss of the Y1003 regulatory binding site for CBL ubiquitin ligase, required for MET degradation and signal attenuation. Loss of the Y1003 binding site of MET results in sustained MET signaling, which has been implicated as an oncogenic driver in a subset of NSCLC. The importance of MET as a driver is demonstrated in xenograft models of NSCLC with METex14del and MET amplification, and where MGCD265 induces tumor regression. Additionally, confirmed partial responses have been observed in pts with NSCLC characterized by METex14del who were treated with MGCD265 in the Phase 1 setting.
Methods:
Pts with platinum pre-treated NSCLC characterized by activating genetic MET alterations identified in tumor tissue or circulating tumor DNA (ctDNA) are eligible for this multi-center, global, Phase 2 trial. Pts are assigned to one of four cohorts based on the type of MET dysregulation and detection method: 1) mutations in tissue, 2) amplification in tissue, 3) mutations in ctDNA, and 4) amplification in ctDNA. The primary endpoint is Objective Response Rate (ORR) in accordance with RECIST 1.1; a Bayesian Predictive Probability Design is applied independently to each cohort. Secondary objectives include safety, tolerability, response duration, survival, correlation between tissue and ctDNA testing, and PK/PD. This study is currently open globally, and recruitment is ongoing.
Results:
Section not applicable.
Conclusion:
Section not applicable.
