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C.A. Vargas
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-060 - Biweekly Irinotecan/Bevacizumab in Heavily Treated Advanced NSCLC and Survival According to TIMP1 and EGFR Expression (ID 2521)
09:30 - 09:30 | Author(s): C.A. Vargas
- Abstract
Background:
Irinotecan and bevacizumab are effective against non-small cell lung cancer (NSCLC) and synergism with non-cross-resistance has been demonstrated in preclinical studies. Tissue inhibitor of metalloproteinases 1 (TIMP1) and EGFR regulates extracellular matrix catabolism and promotion of cell growth and anti-apoptotic activity in NSCLC.
Methods:
Forty nine patients with heavily treated metastatic NSCLC were enrolled from March 2011 to November 2014. Thirty-three (67%) had never been exposed to bevacizumab and 16 had received antiangiogenic therapy as part of their first-line (all had achieved a previous response for more than 6 months). Treatment consisted of a 90-min intravenous infusion of 125 mg/m[2] irinotecan on day 1 and 8 plus 7.5 mg/kg bevacizumab on day 1 (treatment was repeated every 3 weeks). In all patients the mutational status of KRAS and EGFR, as well as TIMP1 and EGFR expression was evaluated.
Results:
The median age was 60 years (range, 44-78 years), 57% was male and 75% had ECOG 0-1. The median follow-up was 13.2 months and twenty-three patients had received >3 prior lines. The ORR was 32% (95%CI 22% to 39%) and thirteen patients (26%) achieve stable disease. Median progression-free survival (PFS) rate was 4.4 months (95%CI 2.8-8.3) and median overall survival (OS) rate was 18.0 months (95%CI 16.2-30.7). Nine patients harbouring EGFR mutations had a long-lasting, partial response (>5 months after at least 4 prior lines). Major toxicity was myelosuppression (grade 3 neutropenia occurred in 32% of patients and thrombocytopenia in 8.3%). Three patients experienced febrile neutropenia, one patient suffered grade 4 diarrhoea, and non-haematological toxicity was usually mild. Shorter OS was found in patients with a higher expression of TIMP1 mRNA (P=0.0001) but not according to the expression of EGFR (P=0.14).
Conclusion:
Irinotecan plus bevacizumab resulted in favourable activity and manageable toxicity profiles as third or fourth line for patients with advanced NSCLC. Our results suggested that such regimen can represent a reasonable chemotherapeutic option, especially for subjects having EGFR mutations and low expression of TIMP1.
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 2
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-028 - BIM Deletion Polymorphisms in Hispanic Patients with Non-Small Cell Lung Cancer Who Carriers EGFR Mutations (CLICaP) (ID 2597)
09:30 - 09:30 | Author(s): C.A. Vargas
- Abstract
Background:
Germline alterations in the proapoptotic protein Bcl-2-like 11 (BIM) can have a crucial role in diverse tumors. To determine the clinical utility of detecting BIM deletion polymorphisms (par4226 bp/ par363 bp) in EGFR positive non-small-cell lung cancer (NSCLC), we examined outcomes of patients (pts) with and without BIM alterations
Methods:
We studied 89 NSCLC pts with EGFR mutation who were treated with erlotinib between January 2009 and November 2014. BIM deletion was analyzed by PCR in formalin-fixed paraffin-embedded (FFPE) tissues of tumor biopsies. We retrospectively analyzed clinical characteristics, response rate, toxicity, and outcomes among patients with and without BIM deletion (del)
Results:
BIM deletion was present in 14 pts (15.7%). There were no significant differences between pts with and without BIM del in clinical characteristics or type of EGFR mutation; however, pts with BIM del had a worse overall response rate to erlotinib (42.9% vs. 73.3% for pts without BIM del; p=0.024) as well as a significantly shorter progression-free survival (PFS) (10.8 del+ vs. 21.7 months for pts without BIM del; p=0.029) and overall survival (OS) (15.5 del+ vs. 34.0 months for pts without BIM del; p=0.035). Multivariate Cox regression analysis showed that BIM deletion was an independent indicator of shorter PFS (HR 3.0; 95%CI 1.2-7.6; p=0.01) and OS (HR 3.4; 95%CI 1.4-8.3; p=0.006)
Conclusion:
The incidence of BIM del found in pts from Colombia is similar to that previously described in Asia; this alteration is associated with a poor clinical response to erlotinib and represents an independent prognostic factor for pts who had NSCLC with EGFR mutations
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P2.04-077 - PDL1 Expression in Metastatic Non-Small Cell Lung Cancer Patients from Colombia (CLICaP) (ID 2839)
09:30 - 09:30 | Author(s): C.A. Vargas
- Abstract
Background:
Programmed cell death-1-ligand 1 (PD-L1) is involved in the ability of tumor cells to escape the host’s immune system. PD-L1 is selectively expressed in a number of tumors. The blockade of interactions between PD-1 and PD-L1 enhances the immune function in vitro and mediates antitumor activity in preclinical models. Recent studies have suggested that antibody-mediated blockade of PD-L1 induced durable tumor regression and prolonged stabilization of the disease in certain cancers including NSCLC. A recent study demonstrated that immunohistochemical (IHC) analysis detected no objective response in PD-L1-negative patients. However, 36% of the patients with PD-L1-positive tumors had a positive response.
Methods:
PD-L1 was assessed by IHC (Dako MAb) in 115 NSCLC patients, considering as positive a staining intensity ≥ 2 in more than 5% of cells. The driver mutation epidermal growth factor receptor (EGFR) was examined by direct sequencing and allele specific PCR. ALK FISH was performed using the Vysis ALK Break-Apart Probe. The correlations of PD-L1 expression with major clinicopathologic parameters and outcomes were analyzed.
Results:
Mean age was 64.3 years (SD+/-10.7), 66% were females, 83% had adenocarcinoma and 58% were former/current smokers. Fourteen patients (18%) had mutations in the EGFR and 19 (25%) were PD-L1+. PD-L1 was positive in fifty-nine patients (51%) and this condition was more frequent in the light or never smokers (p=0.05). In the same way PD-L1 positivity was significantly associated with presence of EGFR mutations (p=0.03), in tumors with a higher grade of differentiation (p=0.023) and in presence of vascular invasion (p=0.038). Patients with positive PD-L1 expresion had a longer progression free survival (PFS) (6.4 months vs. 3.0 months, p= 0.001) and overall survival (OS) (28.2 vs. 12.4 months; p=0.001).
Conclusion:
Although the study sample is small, PD-L1 positivity correlates with PFS and OS. This results supports that PD-L1 might be a critical factor in the use of NSCLC immunotherapy.
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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: 2
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-047 - Weekly Paclitaxel plus Bevacizumab in Heavily Pre-Treated Non-Small-Cell Lung Cancer (NSCLC) Patients (ID 3062)
09:30 - 09:30 | Author(s): C.A. Vargas
- Abstract
Background:
Combination of weekly paclitaxel and bevacizumab showed synergistic effect, anti-tumor efficacy and a good toxicity profile in patients with non small cell lung cancer (NSCLC). We retrospectively reviewed safety and efficacy of this regimen in metastatic non-squamous NSCLC as fourth-line therapy or beyond.
Methods:
Thirty nine patients were included between November 2011 and December 2014; those were bevacizumab eligible and received weekly paclitaxel (80 mg/m[2], days 1, 8 and 15 every 21 days) plus bevacizumab (7.5 mg/kg at day 1) after three prior lines of chemotherapy. Efficacy was evaluated by CT-scan every 10 to 12 weeks and treatment was continued until progression or unacceptable toxicity. Main outcomes were overall response rate (ORR), progression free survival (PFS) and overall survival (OS).
Results:
Median age 61 (44-78), female 51.3%, never smokers 53.8%, ECOG >2 25.6% and more than four previous lines 53.8%. All patients were treated with a first-line platinum-based doublet with (38.5%) or without bevacizumab (61.5%) and all of them received docetaxel as second-line (ORR 33.4/SLP 4.6 months, CI95% 2-6.7). With weekly paclitaxel/bevacizumab the ORR was 36% and 28.2% achieved stable disease for at least 3 months. Median PFS was 5.8 months (CI95% 4.6-7.1) and OS was 18.0 months (CI95% 15.2-34.2). Grade 3-4 adverse events included neutropenia (10%), onycholysis (7.6%) and infection (5%). One patient died from a massive hemoptysis and prolonged responses were observed in two patients who had received bevacizumab as part of first-line chemotherapy and in another one who harbored an ALK rearrangement.
Conclusion:
In this retrospective series, our results suggest that weekly paclitaxel/bevacizumab had a good safety and efficacy profile in heavily pre-treated metastatic NSCLC.
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P3.01-067 - Pemetrexed (P)/Carboplatin/Bevacizumab (B) Followed by Maintenance P/B in Hispanic Patients with Non-Squamous NSCLC (ID 2507)
09:30 - 09:30 | Author(s): C.A. Vargas
- Abstract
Background:
The present study evaluated the efficacy and safety of pemetrexed, carboplatin and bevacizumab, followed by maintenance pemetrexed and bevacizumab, in chemotherapy-naïve patients with stage IV non-squamous non-small cell lung cancer (NSCLC).
Methods:
The patients were administered pemetrexed (500 mg/m[2]), carboplatin (AUC 5.0 mg/ml/min) and bevacizumab (7.5 mg/kg) intravenously every three weeks for up to four cycles. Patients who did not experience tumor progression remained on maintenance pemetrexed and bevacizumab until disease progression or unacceptable toxicity. Primary endpoints were overall response rate (ORR), progression free survival (PFS) and overall survival (OS).
Results:
Hundred forty-four Colombian patients were included and received treatment. The median age was 64 years (range, 32-86 years), 61% was female and 55% had some history of tobacco exposure. The median follow-up was 13.8 months, and the median number of manteinance cycles was 8 (range, 1- 32). Among patients assessable for response, the ORR was 66% (95%CI, 47% to 79%). Median progression-free and overall survival rates were 7.9 months (95%CI 5.9-10.0 months) and 21.4 months (95%CI 18.3 to 24.4 months), respectively. Grade 3/4 hematologic toxicity was anemia (14%), neutropenia (8%), and thrombocytopenia (16%). Grade 3/4 nonhematologic toxicities were proteinuria (2%), venous thrombosis (4%), fatigue (11%), infection (6%), nephrotoxicity (2%), and sensory neuropathy (4%). There was no grade 3 or greater hemorrhagic events or hypertension cases.
Conclusion:
Overall, pemetrexed and carboplatin plus bevacizumab, followed by maintenance pemetrexed and bevacizumab, was effective and tolerable in hispanic patients with non-squamous NSCLC. This regimen was associated with acceptable toxicity and prolonged OS.
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-020 - ALK Rearrangements Epidemiology in Latin America (CLICaP) (ID 2957)
09:30 - 09:30 | Author(s): C.A. Vargas
- Abstract
Background:
Latin American countries are heterogeneous in terms of lung cancer incidence, ethnicity, and exposure to potential carcinogens. The discovery of the echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) translocation as an oncogenic driver has led to the development of novel therapies with activity in vitro and in the clinic. In this study we evaluated the frequency and clinical characteristics of ALK rearrangements in six Latin-American countries.
Methods:
A total of 2799 biopsies of advanced NSCLC patients from 6 countries of Latin America (Argentina, Colombia, Costa Rica, Panama, Ecuador, and Mexico) were evaluated by the method fluorescence in situ hybridization (FISH) for detection of ALK-rearrangements. Demographic and clinicopathologic characteristics were analyzed.
Results:
The FISH analyses showed positive ALK fusion gene status in 6.55% (181/2761) of the total sample from all participating countries. ALK+ for each country was a follows: Argentina 6.08% (105/1726), Colombia 4.83% (10/207), Costa Rica 4.83% (2/49), Mexico 8.57% (64/746), and Panama 0% (0/33). Ecuador only used immunohistochemistry for ALK detection rearrangement; therefore, these samples were excluded from FISH technique analysis.
Conclusion:
The frequency of ALK rearrangement in Latin America is higher than previously reported for the Caucasian and Japanese populations. In addition, there is significant continental variability. Until now, FISH for ALK testing is not widely available in Latin America due to its high cost, time-consumption and result interpretation. There is an increased need to develop a common platform for genomic evaluation in developing countries.
