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R.N. Pillai
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MINI 29 - Meta Analyses and Trial Conduct (ID 156)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:D. Morgensztern, M. Redman
- Coordinates: 9/09/2015, 18:30 - 20:00, Mile High Ballroom 2a-3b
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MINI29.01 - Squamous Cell Carcinoma of Lung in the United States: Analysis of the National Cancer Database (NCDB) (ID 2747)
18:30 - 20:00 | Author(s): R.N. Pillai
- Abstract
Background:
Lung squamous cell carcinoma (SCC) is the second most common histological sub type of lung cancer and accounts for about 30% of all non-small cell lung cancers (NSCLC). We analyzed the NCDB, an oncology outcomes database administered by the American College of Surgeons and the American Cancer Society, to study the epidemiology, patterns of care, outcomes and temporal changes in incidence of SCC.
Methods:
The NCDB was queried from 1998 to 2011 for SCC using ICD-O-3 codes. Temporal changes in incidence were estimated in intervals (1998-1999, 2000-2003, 2004-2007, 2008-2011). The univariate association with covariates between SCC and other subtypes of NSCLC was assessed using Chi-square test or ANOVA. The univariate (UV) and multivariable analysis (MV) with OS were conducted by Cox proportional hazards model and log-rank tests. All statistical analyses were conducted using SAS Version 9.3.
Results:
A total of 435,358 pts with SCC were included in the analysis and accounted for 28% of all NSCLC pts in NCDB. Pt characteristics: median age 70 (18-90 yrs); males 64%; whites 87%; academic centers 27%; metro locations 78%; government insured 72%; Charlson/Deyo comorbidity score (CDS) 0 in 55% and ≥2 in 15%, and stage III/IV- 34/31%. Chemotherapy was used in 39% of pts, radiation in 46% and surgery in 32%. Approximately 19% of the pts did not receive any of the three treatments. Incidence of SCC decreased over time (35%, 28%, 26%, 27%) vs. increasing trend in non-SCC (65%, 72%, 75%, 72%); p<0.001). The trend was similar across all races and sex. SCC was associated with a higher co-comorbidity burden than non-SCC across all stages (CDS 0: 55% vs. 62%; CDS 1: 31% vs. 27%; CDS ≥2: 15% vs. 11%; p<0.001). SCC was associated with inferior 5 yr survival vs. non-SCC in all stages (stage I- 30% vs. 41%, stage II- 16% vs. 21%, stage III- 8.5% vs.10%, stage IV- 1.9% vs. 2.5% respectively; p<0.0001). The 1 yr survival in stage IV SCC is 19.6% vs. 22.2% in non-SCC (p<0.0001). Males had worse survival (HR 1.11 (1.09-1.13; p<0.001). Pts at community centers had worse survival vs. academic centers (HR 1.27 (1.23-1.30; p<0.001). An increasing trend in chemotherapy use was observed (31% in 1998 to 43% in 2011) vs. a decreasing trend in use of radiation (52% in 1998 to 46% in 2011) and surgery (32% in 1998 to 27% in 2011). Chemotherapy was received by 48% of patients with stage IV SCC. Chemotherapy use across other stages: 0/I- 18%, II- 46%, III- 60%. Males were more likely to receive any treatment (OR 1.12 (1.08-1.15); p<0.001). Pts that received any treatment had significantly better 5 year survival than those who did not receive any (20.3% vs. 3.3%, p<0.0001)
Conclusion:
SCC accounted for 28% of all cases of NSCLC in the United States, was associated with higher comorbidities and a significantly worse survival compared to non-SCC of the lung. Chemotherapy was used in only 48% of pts with stage IV SCC.
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ORAL 05 - Surgery (ID 97)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:P. Van Schil, F.(. Kong
- Coordinates: 9/07/2015, 10:45 - 12:15, 201+203
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ORAL05.05 - Trimodality Therapy in the Treatment of Stage IIIA Non-Small Cell Lung Cancer (NSCLC): A National Cancer Database Analysis (ID 2962)
10:45 - 12:15 | Author(s): R.N. Pillai
- Abstract
Background:
Significant controversy remains regarding the care of patients (pts) with clinical stage IIIA NSCLC. While multi-modality therapy is an acceptable strategy in selected pts, the optimal approach is not firmly established. We analyzed outcomes and predictors associated with trimodality therapy (TT) in the National Cancer Database (NCDB), an oncology outcomes database administered by the American College of Surgeons and the American Cancer Society.
Methods:
The NCDB was queried from 2003-2011 for NSCLC pts diagnosed with stage IIIA-N2 disease and treated with chemotherapy and radiation (CRT). Data was extracted on patient demographics, tumor pathology, treatments and outcomes. Three cohorts of pts were studied - CRT only/no surgery (NS), CRT + lobectomy (L) and CRT + pneumonectomy(P). The univariate and multivariable analyses (MV) were conducted using Cox proportional hazards model and log rank tests. All analyses were performed using SAS Version 9.3.
Results:
A total of 29,584 pts were included in this analysis: NS-91.7%, L-7%, and P-1.5%. Pt characteristics: median age 66 years (yrs); males 56%; whites 86%; academic centers 27%; metro locations 78%; government insured 63%; Charlson/Deyo comorbidity score 0 in 66%. Pts < 60 yrs were more likely to receive TT- L (47%), P (60%) vs. NS (29%); p<0.001. Pts in academic centers were more likely to get TT than NS (42% vs. 25%). On MV analysis, L and P had significantly better survival vs. NS: HR 0.43 (0.38-0.48) and HR 0.57 (0.46-0.71) respectively; p <0.001. The median survival of L, P and NS were 44.5 m vs. 25.6 m vs. 15.7 m (p<0.001) and 5- year survival rates (SR) were 44% vs. 33% vs. 14% respectively. 30-day mortality was higher in P vs. L [7% vs. 2.6%; OR 0.26(0.16-0.45); p<0.001]. Pts with <2 lymph nodes (LN) had better survival than pts with >2 LNs in L (50% vs. 37%; 60m vs. 38.8m) but worse in NS (13.8% vs.16.4%; 15.3m vs.18.5m). On MV analysis of LNs, L had better survival than NS: HR 0.4 (0.35-0.46) in <2 LN pts and HR 0.56 (0.46-0.69) in ≥2 LN pts; p<0.001. In pts with <2 LN, L had better survival than P (60m vs. 25.5m; p<0.0001). L and P had better SR than NS in all ages: 48% vs.37% vs. 19% in ≤60 yrs; 42% vs. 30% vs.14% in 61-70 yrs, 36% vs.19% vs. 10% in >70 yrs.
Conclusion:
TT was utilized in less than 10% of pts with stage IIIA-N2 disease, suggesting high degree of pt selection. In this selected group, TT was associated with favorable outcomes relative to CRT alone.
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ORAL 17 - EGFR Mutant Lung Cancer (ID 116)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:P. Meldgaard, E. Felip
- Coordinates: 9/08/2015, 10:45 - 12:15, Four Seasons Ballroom F3+F4
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ORAL17.07 - Mechanisms of Acquired Resistance to AZD9291 in EGFR T790M Positive Lung Cancer (ID 1365)
10:45 - 12:15 | Author(s): R.N. Pillai
- Abstract
Background:
AZD9291 is an irreversible, mutant-selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) developed to have potency against both EGFR-sensitizing mutations and T790M. In the ongoing Phase I study of AZD9291 (AURA, NCT01802632), the response rate in patients with T790M positive lung cancer with disease progression on previous EGFR-TKI was >60%, with a preliminary median progression-free survival of >10 months. The molecular mechanisms underlying acquired resistance to AZD9291 are currently under investigation.
Methods:
Plasma genotyping was performed on patients from AURA who had progressed on AZD9291 if they had detectable T790M pre-AZD9291, as assessed by tumor or plasma genotyping, and if they had plasma collected at progression available for analysis. Cell-free DNA (cfDNA) was extracted from plasma taken at progression. Droplet digital PCR (ddPCR) was performed for EGFR exon 19 deletions, L858R, T790M, and C797S. For further exploration, next-generation sequencing (NGS) of an amplicon panel was performed on available progression cfDNA. Lastly, targeted NGS was performed on available resistance biopsy specimens.
Results:
Plasma specimens were available following disease progression on AZD9291 from 40 patients with tumors positive for T790M through tumor (33) or plasma genotyping (7). Twenty-six progression cfDNA specimens were positive for an EGFR-sensitizing mutation by ddPCR, and were deemed eligible for initial resistance analysis. Of these, 12 (46%) had no detectable T790M in plasma despite presence of the EGFR-sensitizing mutation, suggesting overgrowth of an alternate resistance mechanism. Seven patients had detectable C797S on ddPCR (27%), all with detectable T790M; of 14 with detectable T790M at resistance, C797S was only detected with EGFR exon 19 deletions (7/9) and not L858R (0/5, p=0.02). Plasma NGS was performed on 12 cases with acquired resistance that were T790M positive pretreatment. Exon 19 deletion/T790M/C797S were detected in four cases, with two of these harboring two different DNA mutations encoding for C797S. One case lost T790M and exhibited HER2 copy number gain (6.3 copies); a tumor biopsy from a separate case underwent aCGH at Institute Gustave Roussy and was also found to have focal HER2 amplification with loss of T790M. Targeted NGS was performed on resistance biopsies from a total of 10 patients from four centers with T790M positive biopsies pre-AZD9291. Six cases maintained T790M, with three harboring exon 19 del/T790M/C797S. In four cases with loss of T790M, one harbored BRAF V600E and one harbored PIK3CA E545K.
Conclusion:
Complementary genomic analysis of plasma and tumor DNA provides insight into the diverse molecular mechanisms of acquired resistance to AZD9291 in EGFR-mutant lung cancer. Our studies show that a majority of cases maintained T790M at resistance, at times acquiring a new C797S mutation in those with EGFR exon 19 deletion. Loss of T790M at progression may be mediated by overgrowth of cells harboring HER2 amplification, BRAF V600E, or PIK3CA mutations. These data highlight the need for investigation of combination therapies to effectively prevent or treat the complexity of drug resistance in EGFR-mutant lung cancer.
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P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.08-020 - Survival Impact of Adjuvant Radiation and Chemotherapy in Patients with Typical and Atypical Pulmonary Carcinoids (ID 3054)
09:30 - 17:00 | Author(s): R.N. Pillai
- Abstract
Background:
Adjuvant chemotherapy or radiation is commonly employed after resection of primary pulmonary carcinoid especially for patients with advanced stage disease with expectation of survival benefit. The indication for adjuvant therapy is poorly defined and there are limited data in support of this clinical practice. We therefore evaluated predictors and potential benefit of adjuvant chemotherapy and radiation using the National Cancer Database (NCDB), an oncology outcomes database administered by the American College of Surgeons and the American Cancer Society
Methods:
The NCDB was queried for patients who had undergone surgical resection of pulmonary carcinoid tumors between 2003 and 2006. Patients younger than 18 years and those with incomplete survival data were excluded from this analysis. Overall survival was defined as time from date of definitive surgery to date of death or last follow-up. Univariate and multivariable models were employed to assess for association between patient survival and variables of interest. Gender, age, and race were fit in a multivariable Cox model with treatment, and backward selection criteria (alpha = 0.1) were used to determine whether education, urban/rural, tumor size, income, laterality, insurance, or comorbidity score were included in the model. The proportional hazards assumption was checked for all models.
Results:
We included 4984 eligible patients diagnosed between 2003 and 2006 in the analysis. Post resection adjuvant radiation was administered to 4.2% of the patients; 1.9% received chemotherapy while the remaining patients did not receive any adjuvant therapy. Patients treated with adjuvant chemotherapy or radiation had worse survival at 2 years post surgery (75.7% and 70.8%% respectively) in comparison to patients managed with surgical resection only (94.2%). This survival difference was still significant in multivariable Cox models after adjusting for relevant patient and prognostic factors including gender, age, race, stage, lymph node involvement, tumor size, education level and co-morbidity score (HR: 2.35, 95% CI: 1.43 - 3.85, p<0.001 and HR: 1.97, 95% CI:1.48 - 2.61, p<0.001 for adjuvant chemotherapy and radiation, respectively). Decreased survival persisted in analyses restricted to patients with lymph node involvement (HR 1.58, p 0.084 and 3.21, p<0.001 for chemotherapy and radiation, respectively), and with advanced stage cancer (HR 4.10, p <0.001 and 2.04, p=0.036 and for radiation and chemotherapy, respectively) . Results did not differ by histology
Conclusion:
We observed worse outcomes in patients with typical and atypical carcinoid treated with adjuvant chemotherapy and radiation post surgery. The poor outcome associated with adjuvant therapy may be explained in part by the fact that patients considered for adjuvant therapy are more likely to have advanced stage disease and adverse tumor characteristics. However, contribution from potential toxicities of chemotherapy and radiation cannot be entirely excluded pending additional analysis in propensity-matched cohorts of patients.
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-003 - Patterns of Disease Progression for Stage IV NSCLC While on PD-1 Directed Therapy as Compared to Standard Chemotherapy (ID 3052)
09:30 - 17:00 | Author(s): R.N. Pillai
- Abstract
Background:
Programmed Cell Death 1 (PD-1) inhibitor therapy is now an established therapeutic modality in certain solid malignancies, including non-small cell lung cancer (NSCLC). The purpose of this study is to determine whether disease progression patterns are different between PD-1 inhibitor therapy or chemotherapy in patients with advanced NSCLC.
Methods:
We performed a retrospective analysis of patients who received PD-1 targeted therapies and systemic chemotherapy for advanced NSCLC treated at the Winship Cancer Institute at Emory University. We reviewed demographic data and treatment history of these patients. RECIST criteria were used to evaluate the patients’ baseline tumor burden and their subsequent disease progression from imaging studies (CT, PET/CT, MRI).
Results:
The total cohort included 37 patients with a mean age of 67 years. The PD-1 therapy group included 19 patients (14 males, 5 females), with 9 on MK-3475, 3 on MDPL3280A, and 7 on nivolumab. This group included 3 African Americans and 16 Caucasians. The median number of lines of prior chemotherapy was 3. A comparator group of 18 patients on standard chemotherapy was identified (14 males, 4 females). This group included 8 African Americans and 10 Caucasians. In the PD-1 therapy group, 5 patients had no progression and 14 had disease progression. Of these, 5 progressed at their sites of known cancer (36%), 4 progressed at new sites (28.5%), and 5 progressed at both old and new sites (36%). In the chemotherapy group, 4 patients had no disease progression and 14 had progression. Of those 14, 2 were at old sites only (14%), 4 were at new sites only (29%), and 8 were at both old and new sites (57%). The median time to progression was 3.5 months with PD-1 targeted therapy (range 2-13 months) and 6 months with chemotherapy (range 2-21 months).
Conclusion:
Our data suggests no difference between the progression patterns between PD-1 inhibitor therapy and standard chemotherapy patients. Patients on PD-1 therapy appear to have a shorter time to progression than those on traditional chemotherapy.
