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2 trial of BNC105P with everolimus in metastatic renal cell carcinoma
e26
Abstracts / 51 (2015) e1–e36
Interpretation: Different tumour sizes (2.0 cm or less) in lung adenocarcinoma have different clinical pathological characteristics. Overall survival and 5-year survival for lung adenocarcinoma of 1.0 cm or less was higher than in larger tumours, thus early diagnosis and treatment of micro-sized lung cancer is clinically important.
http://dx.doi.org/10.1016/j.ejca.2015.06.076
P0124 SHORT-TERM AND LONG-TERM OUTCOMES FOR VIDEO-ASSISTED THORACOSCOPIC SURGERY AND OPEN LOBECTOMY: RESULTS FROM STATISTICAL ANALYSIS ADJUSTING FOR TREATMENT SELECTION BIAS X. Wang a, H. Lian a, C.E. Nwogu b, J. D’Cunha c, H. Pang a,d. Department of Biostatistics & Bioinformatics, Duke University Medical Center, Durham, NC, USA, b Roswell Park Cancer Institute, State University of New York at Buffalo, Buffalo, NY, USA, c University of Pittsburgh Medical Center, Pittsburgh, PA, USA, d School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China a
Background: Lack of equipoise limits the feasibility of a randomised study to compare short-term and long-term outcomes between video-assisted thoracoscopic surgery (VATS) and open lobectomy. CALGB observational data from a multi-institutional setting is available for the comparison. Because of the potential bias associated with treatment selection, standard statistical methods can yield biased estimates for treatment effect. We aim to investigate several statistical approaches, including multivariable regression modelling and propensity-score methods, which can be used to adjust for selection bias in the estimation of treatment effect. Methods: 519 patients with stage I and II non-small-cell lung cancer, whose tumours had been collected as part of CALGB lung cancer tissue bank, were eligible to participate. Multivariable regression modelling and propensity score based methods (eg, matching and inverse probability weighting) were used to compare VATS and open lobectomy in terms of the length of post-operative hospital stay and overall survival. Propensity score for treatment selection was estimated via logistic model with age, race, sex, performance status, comorbidities, histology, tumour stage, and size as covariates. Findings: Consistent with the primary findings from Nwogu et al. (2015), all statistical analyses indicate that VATS is associated with significantly shorter length of post-operative hospital stay. Univariate analysis shows VATS has longer overall survival than open lobectomy, but the survival benefit disappears in the multivariable regression and all propensity-score-based methods investigated. Interpretation: Several statistical methods yield consistent results. This multi-institutional study supports the assertion that VATS lobectomy results in shorter hospital length of stay compared with open lobectomy for early stage non-small-cell lung cancer. Survival was similar between the two groups.
P0125 A PHASE 1/2 TRIAL OF BNC105P WITH EVEROLIMUS IN METASTATIC RENAL CELL CARCINOMA S. Pal a,*, A. Azad b, S. Bhatia c, H. Drabkin d, B. Costello e, J. Sarantopoulos f, R. Kanesvaran g, R. Lauer h, C. Sweeney i, N. Hahn j, G. Sonpavde k, S. Richey l, T. Breen m, G. Kremmidiotis n, A. Leske o, E. Doolin p, D. Bibby p, J. Simpson p, J. Iglesias n, T. Hutson p. a City of Hope Medical Center, Duarte, CA, USA, b BC Cancer Agency, Vancouver, BC, Canada, c University of Washington, Seattle, WA, USA, d Medical College of South Carolina, Charleston, SC, USA, e Mayo Clinic, Rochester, MN, USA, f University of Texas Health Science Center, San Antonio, TX, USA, g Singapore National Cancer Center, Singapore, h University of New Mexico Cancer Center, Albuquerque, NM, USA, i Dana Farber Cancer Center, Boston, MA, USA, j Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA, k Deke-Slayton Cancer Center, Webster, TX, USA, l Texas Oncology, Fort Worth, TX, USA, m Hoosier Cancer Research Network, Indianapolis, IN, USA, n Bionomics, Thebarton, SA, Australia, o bioCSL, Melbourne, Australia, p Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA Background: In patients with metastatic renal cell carcinoma (mRCC), everolimus represents a standard of care option for patients who have had prior vascular endothelial growth factor (VEGF)-directed therapy. BNC105P is an inhibitor of tubulin polymerisation and preclinical studies suggest possible synergy with everolimus. In this phase 1/2 study, the efficacy and safety of the combination was explored. Methods: A phase 1 study in patients with clear-cell mRCC and any number of different prior treatments was done using a classical 3+3 design to evaluate standard doses of everolimus with increasing doses of BNC105P (4.2, 8.4, 12.6, and 16 mg/m2). At the recommended phase 2 dose, patients with clear-cell mRCC and one to two prior treatments (including P1 VEGF-TKI) were randomised to BNC105P with everolimus (group A) or everolimus alone (group B). Patients were stratified by MSKCC risk factors and number of prior VEGF-TKIs. The primary endpoint of the study was 6-month progression-free survival. Findings: 15 patients were included in the phase 1 component, and a dose of BNC105P at 16 mg/m2 with everolimus at 10 mg daily was identified as the recommended phase 2 dose. In the phase 2 study, 139 patients were randomised across 77 treatment centres (United States of America (USA): 63; non-USA: 14), with 69 and 67 evaluable patients in groups A and B, respectively. Six-month progression-free survival was similar in the treatment groups (group A: 33.82% versus group B: 30.30%, p = 0.66) and no difference in median progression-free survival was observed (group A: 4.7 months versus group B: 4.1 months; p = 0.49). Most adverse events were consistent with everolimus-related toxic effects. Changes in several biomarkers (matrix metalloproteinase-9, stem-cell factor, sex hormone binding globulin, and serum amyloid A protein) were associated with clinical outcome with BNC105P. Conclusions: Although the primary endpoint was not met in an unselected population, intriguing correlative studies suggest several potentially predictive biomarkers. Further prospective assessment of BNC105P in relevant biomarker-based subsets is warranted.
http://dx.doi.org/10.1016/j.ejca.2015.06.077 http://dx.doi.org/10.1016/j.ejca.2015.06.078
Abstracts / 51 (2015) e1–e36
Interpretation: Different tumour sizes (2.0 cm or less) in lung adenocarcinoma have different clinical pathological characteristics. Overall survival and 5-year survival for lung adenocarcinoma of 1.0 cm or less was higher than in larger tumours, thus early diagnosis and treatment of micro-sized lung cancer is clinically important.
http://dx.doi.org/10.1016/j.ejca.2015.06.076
P0124 SHORT-TERM AND LONG-TERM OUTCOMES FOR VIDEO-ASSISTED THORACOSCOPIC SURGERY AND OPEN LOBECTOMY: RESULTS FROM STATISTICAL ANALYSIS ADJUSTING FOR TREATMENT SELECTION BIAS X. Wang a, H. Lian a, C.E. Nwogu b, J. D’Cunha c, H. Pang a,d. Department of Biostatistics & Bioinformatics, Duke University Medical Center, Durham, NC, USA, b Roswell Park Cancer Institute, State University of New York at Buffalo, Buffalo, NY, USA, c University of Pittsburgh Medical Center, Pittsburgh, PA, USA, d School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China a
Background: Lack of equipoise limits the feasibility of a randomised study to compare short-term and long-term outcomes between video-assisted thoracoscopic surgery (VATS) and open lobectomy. CALGB observational data from a multi-institutional setting is available for the comparison. Because of the potential bias associated with treatment selection, standard statistical methods can yield biased estimates for treatment effect. We aim to investigate several statistical approaches, including multivariable regression modelling and propensity-score methods, which can be used to adjust for selection bias in the estimation of treatment effect. Methods: 519 patients with stage I and II non-small-cell lung cancer, whose tumours had been collected as part of CALGB lung cancer tissue bank, were eligible to participate. Multivariable regression modelling and propensity score based methods (eg, matching and inverse probability weighting) were used to compare VATS and open lobectomy in terms of the length of post-operative hospital stay and overall survival. Propensity score for treatment selection was estimated via logistic model with age, race, sex, performance status, comorbidities, histology, tumour stage, and size as covariates. Findings: Consistent with the primary findings from Nwogu et al. (2015), all statistical analyses indicate that VATS is associated with significantly shorter length of post-operative hospital stay. Univariate analysis shows VATS has longer overall survival than open lobectomy, but the survival benefit disappears in the multivariable regression and all propensity-score-based methods investigated. Interpretation: Several statistical methods yield consistent results. This multi-institutional study supports the assertion that VATS lobectomy results in shorter hospital length of stay compared with open lobectomy for early stage non-small-cell lung cancer. Survival was similar between the two groups.
P0125 A PHASE 1/2 TRIAL OF BNC105P WITH EVEROLIMUS IN METASTATIC RENAL CELL CARCINOMA S. Pal a,*, A. Azad b, S. Bhatia c, H. Drabkin d, B. Costello e, J. Sarantopoulos f, R. Kanesvaran g, R. Lauer h, C. Sweeney i, N. Hahn j, G. Sonpavde k, S. Richey l, T. Breen m, G. Kremmidiotis n, A. Leske o, E. Doolin p, D. Bibby p, J. Simpson p, J. Iglesias n, T. Hutson p. a City of Hope Medical Center, Duarte, CA, USA, b BC Cancer Agency, Vancouver, BC, Canada, c University of Washington, Seattle, WA, USA, d Medical College of South Carolina, Charleston, SC, USA, e Mayo Clinic, Rochester, MN, USA, f University of Texas Health Science Center, San Antonio, TX, USA, g Singapore National Cancer Center, Singapore, h University of New Mexico Cancer Center, Albuquerque, NM, USA, i Dana Farber Cancer Center, Boston, MA, USA, j Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA, k Deke-Slayton Cancer Center, Webster, TX, USA, l Texas Oncology, Fort Worth, TX, USA, m Hoosier Cancer Research Network, Indianapolis, IN, USA, n Bionomics, Thebarton, SA, Australia, o bioCSL, Melbourne, Australia, p Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA Background: In patients with metastatic renal cell carcinoma (mRCC), everolimus represents a standard of care option for patients who have had prior vascular endothelial growth factor (VEGF)-directed therapy. BNC105P is an inhibitor of tubulin polymerisation and preclinical studies suggest possible synergy with everolimus. In this phase 1/2 study, the efficacy and safety of the combination was explored. Methods: A phase 1 study in patients with clear-cell mRCC and any number of different prior treatments was done using a classical 3+3 design to evaluate standard doses of everolimus with increasing doses of BNC105P (4.2, 8.4, 12.6, and 16 mg/m2). At the recommended phase 2 dose, patients with clear-cell mRCC and one to two prior treatments (including P1 VEGF-TKI) were randomised to BNC105P with everolimus (group A) or everolimus alone (group B). Patients were stratified by MSKCC risk factors and number of prior VEGF-TKIs. The primary endpoint of the study was 6-month progression-free survival. Findings: 15 patients were included in the phase 1 component, and a dose of BNC105P at 16 mg/m2 with everolimus at 10 mg daily was identified as the recommended phase 2 dose. In the phase 2 study, 139 patients were randomised across 77 treatment centres (United States of America (USA): 63; non-USA: 14), with 69 and 67 evaluable patients in groups A and B, respectively. Six-month progression-free survival was similar in the treatment groups (group A: 33.82% versus group B: 30.30%, p = 0.66) and no difference in median progression-free survival was observed (group A: 4.7 months versus group B: 4.1 months; p = 0.49). Most adverse events were consistent with everolimus-related toxic effects. Changes in several biomarkers (matrix metalloproteinase-9, stem-cell factor, sex hormone binding globulin, and serum amyloid A protein) were associated with clinical outcome with BNC105P. Conclusions: Although the primary endpoint was not met in an unselected population, intriguing correlative studies suggest several potentially predictive biomarkers. Further prospective assessment of BNC105P in relevant biomarker-based subsets is warranted.
http://dx.doi.org/10.1016/j.ejca.2015.06.077 http://dx.doi.org/10.1016/j.ejca.2015.06.078