Virtual Library
Start Your Search
Victoria Meucci Villaflor
Author of
-
+
P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
-
+
P1.01-49 - Serial Changes in Whole-Genome Cell-Free DNA (cfDNA) to Identify Disease Progression Prior to Imaging in Advanced NSCLC (ID 2484)
09:45 - 18:00 | Author(s): Victoria Meucci Villaflor
- Abstract
Background
Response to treatment in advanced lung cancer is usually determined by clinical and imaging assessment. We analyzed longitudinal changes in blood whole-genome cfDNA to investigate whether a molecular response assessment could provide potentially actionable information prior to imaging.
Method
We prospectively enrolled and serially collected blood from 35 patients with advanced non-small cell lung cancer (NSCLC). Baseline blood samples were drawn prior to initiation of a new treatment and at one or two additional time points, after the first cycle (median 21 days) and the second cycle (median 42 days). 4 mL of plasma was separated from peripheral blood collected in Streck tubes. Next, cfDNA was isolated from plasma and used to prepare libraries (15 with bisulfite conversion) for whole-genome sequencing at approximately 20X depth. Based on a patient-specific profile of whole-genome features, changes in the fraction of tumor-derived cfDNA were quantified over the initial course of treatment. Imaging was performed per standard practice with treatment response determined by an independent radiologist according to RECIST guidelines.
Result
Median age of patients was 72 (range 48-87), and 49% were female. 69% of patients were on their first line of therapy (range 1-5). Patients were treated with an immune checkpoint inhibitor +/- chemotherapy (22), chemotherapy alone (11), or targeted therapy (2). Patients with predicted progression by cfDNA (n=4), indicated by an increase in tumor fraction at either post-treatment blood collection, had worse progression-free survival (PFS) compared to patients who did not show an increase (n=31) (hazard ratio 22.3, [95% CI 3.9-127.8], log-rank p=9 x 10-7). For the patients who were predicted to progress, the cfDNA assay preceded clinical evaluation by a median of 34 days. Median PFS was 56 days for patients with predicted progression versus 370 days for others. All patients with predicted progression were later confirmed to progress at the first follow-up evaluation (4/4, 100% positive predictive value). For the remaining patients, 27 of 31 did not progress (87% negative predictive value). Therefore, sensitivity for the assay was 50% and specificity was 100%.
Conclusion
Analyzing tumor-derived cfDNA early in the course of a new therapy holds promise to identify patients with early disease progression across multiple types of treatment. This technology may enable early switching to other potentially effective therapies, increasing the value proposition of all delivered treatment.
-
+
P1.01-67 - Ph I/II Carboplatin, Nab-Paclitaxel and Pembrolizumab for Advanced NSCLC (HCRN LUN13-175): Outcomes by Nab-Paclitaxel Dose (ID 530)
09:45 - 18:00 | Author(s): Victoria Meucci Villaflor
- Abstract
Background
Combination chemotherapy and immunotherapy have significantly improved survival for patients with treatment-naïve advanced non-small cell lung cancer (NSCLC). We sought to evaluate the safety and efficacy of adding pembrolizumab to a standard regimen at the time of study development, nab-paclitaxel and carboplatin. Safety data from phase I have been reported, and phase II commenced with the same chemotherapy doses and flat dosing of pembrolizumab at 200 mg.
Method
Patients with treatment-naïve, stage IIIB/IV NSCLC AJCC 7 (all histology), any PDL1, no EGFR or ALK, ECOG 0-1, received carboplatin AUC 6 day 1, nab-paclitaxel 100 mg/m2 days 1, 8, 15, and pembrolizumab 200 mg day 1 q21 days for 4 cycles followed by maintenance pembrolizumab q3wks. Co-primary endpoints were progression-free survival (PFS) and response rate (RR). PDL1 was assessed prior to treatment and from biopsies obtained after cycle 4.
Result
46 patients enrolled, 14 on phase I and 32 in phase II, from June 2015–July 2018. Accrual stopped after data was presented from similar phase III trials. 43 were evaluable for the primary endpoints. Median age was 65 years, 48% female, 45% adenocarcinoma, 94% current/former smokers, 9% brain metastases. PDL1 expression (TPS) by <1%, 1-49%, and ≥ 50% cutoffs was 44%, 28%, and 28%, respectively. ORR was 28%. Median PFS was 5.6 months (CI, 4.2-10.5 mo). Median OS was 15.7 mo (CI 11.1-22.3 mo). There was no statistical differences in PFS or OS outcomes by PDL1 status. Paired PDL1 results from pre- and post-treatment biopsies were available in 8 patients. PDL1 status changed categories in 4/8 samples (n=3, 0% to positive; n=1, 99% to 0%). The most common grade 3-4 adverse events (AEs) were neutropenia (64%), anemia (31%), thrombocytopenia (24%), leukopenia (16%) and fatigue (11%). Other notable AEs included rash (58%), diarrhea (47%), neuropathy (22%), arthralgia (18%), transaminitis (13%), and myalgia (11%). 18% discontinued treatment due to AEs. In an exploratory analysis, there was no difference in median PFS for those receiving total nab-paclitaxel dose of 400–799 mg/m2 compared to ≥800 mg/m2 (6.2 mo vs. 8.2 mo, p=0.62).
Conclusion
Although the study did not meet its pre-specified endpoints of PFS 9 months and RR of 50%, results were similar to previously reported phase III Keynote 407 (squamous histology). Despite hematologic toxicity, the combination could safely be administered, and outcomes were similar for those receiving moderate doses of nab-paclitaxel compared to those with an average of at least 200 mg/m2 per cycle.
-
+
P1.03 - Biology (ID 161)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
-
+
P1.03-38 - EGFR Mutation Status as a Prognostic Marker in Stage 1 Lung Adenocarcinoma After Definitive Surgical Resection (Now Available) (ID 646)
09:45 - 18:00 | Author(s): Victoria Meucci Villaflor
- Abstract
Background
With tumor molecular genetics at the forefront of precision medicine, EGFR mutation status has been paramount for predicting response to therapy in advanced and metastatic NSCLC. However, little is known about the implications of EGFR mutation status in stage 1 disease following definitive surgical therapy, particularly in regard to prognosis and disease recurrence.
Method
We retrospectively studied the clinical outcomes in 101 EGFR-positive patients and 97 age-matched EGFR-negative controls with stage 1 lung adenocarcinoma who underwent definitive surgical resection +/- chemoradiation. EGFR status was determined by pathologic molecular testing performed at time of diagnosis and TNM stage was determined at time of treatment. These cases were then followed for pathologically confirmed cases of recurrence and assessed for stage at recurrence, time elapsed since definitive treatment, and disease-free survival at 1, 2 and 5 years.
Result
EGFR-positive disease demonstrated higher rates of metastatic recurrence with 15% vs 3% in controls (p=0.007). Median time to progression among those who progressed, defined as time to recurrence or death, was significantly shorter in EGFR-positive cases (82 weeks vs 158 weeks, p=0.048). There was no significant difference in rates of recurrence (p=0.32) between both groups. Disease-free survival in EGFR-positive cases was most notably lower at 2 years, with 0.86 (0.78-0.94) vs 0.94 (0.89-0.99).
Conclusion
This study suggests that EGFR-positive disease may be associated with a higher risk of metastatic recurrence and decreased time to progression in individuals who ultimately progress. EGFR molecular testing may be a promising tool for risk stratification and surveillance following definitive management for stage 1 disease. Future prospective modeling may be indicated in this disease.
-
+
P1.17 - Treatment of Early Stage/Localized Disease (ID 188)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
-
+
P1.17-40 - Clinical Implications of Using Circulating Tumor DNA to Assess Minimal Residual Disease (MRD) in Patients with NSCLC After Definitive Treatment (ID 1801)
09:45 - 18:00 | Author(s): Victoria Meucci Villaflor
- Abstract
Background
Circulating tumor DNA (ctDNA) has been used to identify driver genomic alterations during treatment of metastatic nonsmall cell lung cancer (NSCLC). Recent studies have also demonstrated the role of ctDNA to monitor response to therapy. Here we performed an analysis on a cohort of NSCLC patients (pts) with localized disease who underwent ctDNA testing after definitive treatments to determine whether ctDNA can be used as a marker of MRD.
Method
Between 2015-2019, 70 pts with localized NSCLC received ctDNA testing. ctDNA testing was done using the next generation sequencing (NGS) panel of 73 genes via digital sequencing technology (Guardant360). Statistical analysis was performed to determine which factors were associated with ctDNA levels and recurrence free survival (RFS).
Result
Of the 70 pts analyzed, 26 pts had ctDNA testing performed after definitive treatment. Median duration of follow up was 22 months (range: 3 to 36). 26% (n = 7) had stage I disease, 30% (n = 8) had stage II disease, and 42% (n = 11) had stage III disease. 81% (n = 21) were adenocarcinoma while 19% (n = 5) were squamous cell carcinoma. 42% (n = 11) had no recurrence during our observation time, while 58% (n = 15) experienced progression. For definitive treatments, 38% (n = 10) underwent surgery alone, 35% (n = 9) underwent surgery with adjuvant chemotherapy, 15% (n = 4) underwent chemoradiation therapy, 8% (n=2) underwent surgery followed by radiation, and 4% (n=1) under went surgery with adjuvant chemoradiation prior to their ctDNA levels [variant allele frequency (VAF)] being drawn. Of these, 15% (n = 4) tested negative for any ctDNA, while 85% (n = 22) were positive. Only one of the pts with undetectable levels of ctDNA experienced recurrence of cancer 34 months after definitive treatment with surgery followed by chemotherapy. 13 among 22 pts with detectable ctDNA had recurrence (median time to recurrence = 6.3 months). Kaplan-Meir survival analysis revealed a trend toward significant association between the presence of detectable ctDNA and RFS (p = 0.10).
Conclusion
Our analysis demonstrates that ctDNA could potentially be used as a marker to assess MRD following definitive treatment for localized NSCLC.
-
+
P2.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 187)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
-
+
P2.16-21 - Effects of Molecular Markers on Responses, Relapses, and Survival in Lung Cancer Patients with HIV (Now Available) (ID 2038)
10:15 - 18:15 | Author(s): Victoria Meucci Villaflor
- Abstract
Background
Patients with HIV are aging due to potent combination antiretroviral therapy (ART) and the incidence of lung cancer has increased. Limited research has been performed on the relationship between HIV and lung cancer prognosis and recurrence. Based on previous data and our clinical experience, patients with HIV and lung cancer have worse prognosis1 potentially due to social and behavioral risk factors, unfavorable molecular markers and differences in treatment patterns.
Method
We identified patients with HIV and lung cancer between January 1, 2001 and December 31, 2015 using Northwestern Medicine (NM) Electronic Data Warehouse (EDW). Lung cancer cases were verified and treatment/outcome information was extracted by chart review. We then compared the effects of molecular markers on treatment responses, relapses, and survival in lung cancer patients with HIV infection. Incidence and prognosis were compared to historical, non-HIV lung cancer controls.
Result
We included 36 individuals with HIV and lung cancer in this analysis. The median age at diagnosis was 55 years, 75.0% (27/36) were male, 94.0% (34/36) smokers.
Histology:
Small Cell – 1 (2.8%), Squamous cell – 10 (27.8%), Adenocarcinoma – 21 (58.3%), Other NSCLC – 2 (5.6%) Unreported – 2 (5.6%).
Molecular:
EGFR – 2 (5.6%), ROS1 – 0 (0%), ALK – 3 (8.3%), KRAS – 1 (2.8%), PDL1 – 2 (5.6%), Not Reported – 6 (16.7%).
Stage at Diagnosis:
Stage I – 3 (8.3%), Stage II – 6 (16.7%), Stage III – 2 (5.6%), Stage IV – 21 (58.3%), unreported – 4 (11.1%)
Median survival – 2 years for all patients.
EGFR – 1 year, ALK – 5.5 years, KRAS – 1 year, PDL1 – 1 year
Conclusion
In prior research, patients with HIV and lung cancer appear to have decreased survival with reported overall survival of 7 months compared to 25 months for historical controls irrespective of stage and stage appropriate treatment for lung cancer2. In our study cohort, patients appeared to be treated similar to non-HIV controls, and the overall survival is fairly consistent with historic non-HIV controls, but smoking incidence (34/36; 94%) was higher than in non-HIV patients with lung cancer (85%). The prevalence of ALK translocation (3/36; 8%) was higher than typically observed among those without HIV (3-5%) and occurred exclusively in smokers. Typically, ALK translocation occurs in non-smokers. HIV patients treated with ALK inhibitors appeared to respond to similarly to non-HIV patients with NSCLC based on historic clinical data.
Increased mortality in HIV, lung cancer patients is likely multifactorial, including concerns for lack of aggressive anti-cancer therapy delivered in this population. Our findings suggest that identifying driver mutations and molecular marker mutations may improve clinical practice for treatment of HIV-associated lung cancer. More prospective study is needed in this population.
