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O. Macedo-Pérez
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P1.06 - Poster Session with Presenters Present (ID 458)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.06-007 - Radical Treatment of Synchronous Oligometastatic Non-Small Cell Lung Cancer (NSCLC) (ID 6283)
14:30 - 14:30 | Author(s): O. Macedo-Pérez
- Abstract
Background:
Cancer represents a large biological spectrum of disease ranging from localized to multisystem involvement with multiple intermediate stages. Oligometastatic NSCLC is thought to carry a better overall survival (OS) but there are few prospective studies that evaluate it.
Methods:
Prospective cohort study with NSCLC patients treated at the Instituto Nacional de Cancerologia of Mexico, with stage IV and oligometastatic disease (≤ 5 metastatic lesions). Patients were enrolled to receive, after 4 cycles of systemic treatment with platinum-doublet chemotherapy or 4 months of tyrosine kinase inhibitors in patients with driver mutations, local consolidative treatment for the primary lesion and their metastases with chemoradiotherapy, surgery, radiotherapy, stereotactic radiosurgery or radiofrequency ablation based on the decision of the Multidisciplinary Thoracic Committee of the institution. The primary outcome was overall survival. The study was approved by de Institutional Ethics Committee and registered in clinical trials NCT02805530.
Results:
Up to this moment, we have evaluated 29 patients with NSCLC and oligometastatic disease. Of these, 62% males with a median age of 58 years (IQR 52.5-64.5), median CEA 10.2 (IQR 3.25-55), 59% former or currently smokers (median 37.5 package/year), wood-smoke exposure 28%. Overall 90% of the patients presented adenocarcinomas, 28% EGFR mutation (50% deletion of exon 19, 38% mutation on exon 21). At diagnosis 93% of the patients had symptoms mainly cough (48%), dyspnea (30%), neurologic symptoms (26%), weight loss (18%) and dysphonia (15%). We evaluated the oligometastatic disease status with PET-CT and MRI in 66% of the patients and the remaining with CT scan plus MRI. At diagnosis 66% had one or two metastases, 14% three to four metastases and 20% five metastases. For metastatic sites CNS was the main site of metastases in 52% of patients, 28% contralateral lung, 17% bone metastases and 7% at suprarenal. For radical treatment to the primary tumor, 59% chemoradiotherapy, 21% radiotherapy, 28% surgery and 3% radiofrequency. For definite treatment for the metastases, 45% received radiotherapy, 14% chemoradiotherapy and 17% surgery. The mean dose of radiotherapy received for the control of the primary tumor was 56.3 Gy (SD 11.28 Gy) and 29.5 Gy (SD 3.84Gy) for metastases. After multimodal treatment 24% had radiologic complete response. The median OS were 18.26 months (95%CI:10.89-25.64), the median OS for those with and without radiologic complete response were 28.58 months (95%CI:12.98-44.18) and 14.45 months (95%CI:10.40-18.51) respectively.
Conclusion:
Patients with oligometastatic NSCLC with agressive treatment have a large OS regardless their mutational status.
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 3
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-003 - Mutation Profile & Histology According to ERS/ATC/IASCL Associated with IPFS to WBI in BM Patients with Recent Adenocarcinoma Lung Cancer (ID 5817)
14:30 - 14:30 | Author(s): O. Macedo-Pérez
- Abstract
Background:
Brain-metastases (BM) are a common metastatic site in non-small-cell lung cancer (NSCLC). We studied the impact of genetic alterations (EGFR, ALK and KRAS) in relation to objective response rate (ORR), intracranial-progression-free survival (IPFS) and overall-survival (OS) after whole-brain irradiation (WBI) in patients at recently diagnosis with NSCLC and BM.
Methods:
From 2009-2015, 231 NSCLC patients with BM were reviewed for eligibility. Among them, 121 patients with recently diagnosis of NSCLC, were treated with WBI and have available genotyping status.
Results:
EGFR, KRAS, ALK and WT patients were found in 38.0%, 6.6%, 5.8% and 49.6%, respectively. Overall, ORR and disease control rate (DCR) were 62.0% and 76.8%, respectively. ORR for EGFR, KRAS, ALK and WT patients were 82.6%, 25.0%, 71.4% and 50.0%, respectively (p=0.001). Female gender (OR 2.22 [95% CI: 1.01 – 4.89] P=0.047) and EGFR were associated to better response to WBI (OR 5.67 [95% CI 2.0-15.8], P = 0.001). A high architectural histological grade was independently associated with resistance to WBI. Median IPFS was 9.06 months [95% CI 6.5 -11.4]. IPFS for EGFR, K-RAS,ALK and WT patients were 11.9, 4.6,12.5 and 6.6 months, respectively (P <0.0001). EGFR mutation status (HR 0.54 [95%CI 0.3-0.9], P = 0.030) was the only factor associated with higher IPFS in the multivariate Cox-regression analysis. Median OS was 16.6 months [95% CI 11.6-22.6]. OS for EGFR, ALK, KRAS and WT patients were 26.8, 13.5, 4.9 and 13.6 months, respectively (P < 0.001). Intracranial OR was associated with a higher OS (HR 0.28 [95%CI 0.2-0.5], P < 0.001), while KRAS mutation positive status (HR 3.45 [95%CI 1.4-8.4], P = 0.006) was independently associated with worse OS. Figure 1
Conclusion:
EGFR mutation is an independent predictive factor for OR to WBI for BM in patients with NSCLC. KRAS mutation is an independent predictive factor for worse OS after BM.
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P2.03b-083 - Soluble Angiogenic Factors as Predictive Biomarkers of Response to Docetaxel plus Nintedanib as Second Line Therapy in NSCLC (ID 5199)
14:30 - 14:30 | Author(s): O. Macedo-Pérez
- Abstract
Background:
Angiogenesis is fundamental for progression in non-small cell lung cancer (NSCLC). Nintedanib is a potent, triple angiokinase inhibitor of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF). We evaluated the association between plasma levels of VEGF, FGF, and PDGF, both baseline and after treatment with Nintedanib plus Docetaxel, as well as disease control rate (DCR), progression-free survival (PFS) and overall survival (OS), among patients with NSCLC.
Methods:
Thirty-eight patients were enrolled from July 2014 through October 2015. Stage IIIB/IV NSCLC patients who had progression after first-line chemotherapy with adenocarcinoma histology were included. Patients received Docetaxel 75mg/m2 on day 1 plus 200mg of Nintedanib orally twice daily on days 2-21 every three weeks until unacceptable adverse events or disease progression. Peripheral blood samples were taken at baseline and after completion of the second cycle of Docetaxel plus Nintedanib therapy to measure angiogenic factors.
Results:
Mean age at diagnosis was 58.7 years. Eighty-two percent of the patients had metastatic disease, and a good (<2) ECOG performance status (97.4%). Acinar (21.1%) and papillary (15.8%) sub-histological types were the most common adenocarcinoma predominant patterns. Overall response rate and DCR were of 7.9% and 47.3%, respectively. Baseline values of FGF, VEGF and PDGF were 27.6 pg/ml; 122.7 pg/ml and 8,655 pg/ml. Patients with DCR were more likely to have lower median serological values of FGF at follow-up (33.1 vs. 88.1 pg/ml; p=0.0017). Median PFS was 3.7 months. Both in the univariate and multivariate analyses, a higher percentage change reduction in PDGF after treatment was associated with a longer PFS (6.37 vs. 3.58 months, p=0.059; Hazard ratio (HR): 3.15, p=0.024). OS of patients was 8.8 months. Both in the univariate and mutivariate analysis a higher percentage change in FGF was associated with a longer OS (13.8 vs. 7.16 months, p=0.006; HR: 3.63, p=0.033].
Conclusion:
A higher reduction of plasma levels of FGF and PDGF was associated with better clinical outcomes.
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P2.03b-088 - PET-CT with 68Ga-RGD as Biomarker of Response to Nintedanib plus Docetaxel as Second Line Therapy in NSCLC (ID 5196)
14:30 - 14:30 | Author(s): O. Macedo-Pérez
- Abstract
Background:
Nintedanib, an approved second-line treatment for NSCLC in combination with docetaxel, is an oral angiokinase inhibitor against pro-angiogenic pathways. Advanced techniques in nuclear medicine have developed new radiotracers, such as Ga68-RGD for assessment of tumor vascularity and therapy response. The αVβ3 integrin is a transmembrane protein of great importance in tumor angiogenesis, due to its massive overexpression. Peptides containing the RGD sequence have high affinity for αVβ3 integrin receptors overexpressed in tumor cells. We evaluate objective-response rate (ORR), disease-control rate (DCR) by RECIST v.1.1, progression-free survival benefit (PFS) and overall survival (OS) obtained by Nintedanib plus Docetaxel therapy, and its response measured by PET-CT with Ga68-RGD biomarker.
Methods:
Study enrollment from July 2014 to October 2015. Inclusion criteria were confirmed adenocarcinoma histology, and disease progression after platinum-based-chemotherapy. Thirty-eight patients were assigned to receive Docetaxel (75mg/m2, IV) on day 1 plus Nintedanib (200mg, orally twice daily) on days 2-21 every three weeks until unacceptable adverse events or disease progression. All patients underwent a PET-CT with IV tracer Ga68-RGD and measurements at three time points (30, 60 and 120 mins) prior treatment start and after completing 2 therapy cycles.
Results:
Mean age at diagnosis was 58.7±11.4 years. Of the 38 patients, 31 had complete data for analysis. After 2 treatment cycles, the PET-CT assessment response, based on baseline Lung/Spleen SUVmax index, showed an ORR of 7.9% and DCR of 47.3%. Median PFS of 3.7 months and median Hypertensive patients were more likely to have a higher PFS (6.3 vs. 3.3 months; p=0.023), as well as patients with a larger baseline tumoral-volume by Ga68-RGD PET-CT (2.1 vs. 6.1 months; p=0.007). Global OS was of 8.8 months. Non-smokers were more likely to have larger OS (9.3 vs 4.2; p=0.008). Also a median OS was longer among patients with higher Lung/Spleen SUVmax index percentage change after treatment (9.4 vs. 4.9 months; p=0.05) was found.
Conclusion:
A larger baseline tumoral-volume can be associated to a higher progression-free survival due to the major cellular component to target with antiangiogenic therapy, as well as a strong association of larger survival assessed by the Lung/Spleen SUVmax index after treatment, marked by the Ga68-RGD radiotracer.
