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Quantifying the transition from active surveillance to watchful waiting in men with very low-risk prostate cancer
S188
Abstracts
group and number of prior VEGFR TKIs (1 or 2). The study was designed to detect a HR for OS of 0.75 (80% power, 2-sided a = 0.04). Results: A total of 658 patients were randomized from Aug 2013 to Nov 2014. As of 31 Dec 2015, with a minimum follow-up of 13 months, 74 (22%) vs 25 (8%) of patients remained on cabo and eve, respectively (Choueiri Lancet Oncol 2016). A total of 320 deaths were recorded (140 for cabo and 180 for eve). The secondary endpoint of improved OS with cabo was met with a p-value of 0.0003, which surpassed the critical boundary of 0.0163 for this analysis. Median OS was significantly prolonged with cabo (21.4 months vs 16.5 months with eve, HR 0.66, 95% CI 0.53–0.83). Landmark estimates of survival at 18 months were 58% in the cabo arm vs 47% in the eve arm. Improvement in OS with cabo was observed in all prespecified subgroups, including MSKCC risk group, number and type of prior VEGFR TKIs, prior anti-PD-1/PD-L1 treatment, location and extent of tumor metastases, and tumor MET expression level. The percent of patients receiving subsequent anticancer therapy was similar in both arms. Safety results were consistent with the previously-reported safety profiles in this population. Conclusions: Significant improvements in OS, PFS, and ORR were observed with cabo in the Phase 3 METEOR trial of previously-treated patients with advanced RCC. Cabo is an important new treatment option for this patient population. Conflict of interest: Ownership: K. Peltola: Faron Pharmaceuticals; D.T. Aftab: Exelixis, Inc.; C. Scheffold: Exelixis, Inc.; G. Schwab: Exelixis, Inc. Advisory Board: R.J. Motzer: Novartis, Exelixis, Eisai, Pfizer; N.M. Tannir: BMS, Exelixis, Nektar, Novartis, Pfizer, Argos, Calithera; P.N. Mainwaring: Astellas, Medication, Janssen Oncology; J.L. Lee: Roche, Astellas; T.E. Hutson: Speakers’ Bureau: Pfizer, Novartis, Bayer, BMS. Corporate-sponsored Research: M. Schmidinger: Pfizer, Roche; R.J. Motzer: Research for clinical trial support to employer (MSKCC), Pfizer, Novartis, Genentech, Roche; T. Powles: Exelixis, Inc., Novartis, GSK, Genentech; N.M. Tannir: BMS, Exelixis, Epizyme, Novartis, Miranti; B.I. Rini: Pfizer, BMS, Accerleron, Immatics, Peleton; H.J. Hammers: sfj, BMS, Exelixis, Newlink, Pfizer, GSK, Tracon; F. Donscov: Novartis, GSK, Pfizer; B. Roth: Exelixis, Inc. (institutional support only); J.L. Lee: Roche, Pfizer, AstraZeneca, Novartis, Johnson and Johnson, BMS; S. Pal: Pfizer, Bayer, BMS; T.E. Hutson: Pfizer, Novartis, Bayer, BMS. Other Substantive Relationships: M. Schmidinger: Honoraria (Pfizer, Roche, BMS, Novartis), Consulting or Advisory Role (Pfizer, Roche, Novartis, BMS, Exelixis); T. Powles: Consulting or Advisory Role (Exelixis, Inc., Novartis, GSK); B. Escudier: Honoraria and Consulting or Advisory Role (Novartis, GSK, Pfizer, Bayer, Exelixis); B.I. Rini: Consulting or Advisory Role (Pfizer, Roche, BMS, Acceleron, Novartis, GSK), Travel, Accomodations, Expenses (Pfizer); H.J. Hammers: Consulting or Advisory Role (BMS, Exelixis, Pfizer, Cerulean); K. Peltola: Employee (Orion Pharma [Part-time]), Honoraria (Lilly, BMS, Sanofi, Pfizer, Novartis), Consulting or Advisory Role (Lilly, BMS, Baxalta, Sanofi, Pfizer, Novartis), Travel, Accomodations, Expenses (BMS, Novartis, Pfizer); D.Y.C. Heng: Consulting or Advisory Role (Pfizer, Novartis, BMS, Exelixis); D.T. Aftab: Employee (Exelixis, Inc.); C. Hessel: Employee (Exelixis, Inc.); G. Schwab: Employee, Officer of the company (Exelixis, Inc.); T.E. Hutson: Honoraria (Pfizer, Novartis, Bayer, BMS), Consulting or Advisory Role (Pfizer, Novartis, Bayer, BMS, Eisai, Exelixis, Inc.); T.K. Choueiri: Consulting or Advisory Role (Pfizer, GSK, Novartis, Merck, Bayer, Eisai, Roche, Prometheus Labs Inc, BMS, Foundation Medicine Inc.). 2118 ORAL Quantifying the transition from active surveillance to watchful waiting in men with very low-risk prostate cancer M. Van Hemelrijck1 , H. Garmo1 , L. Lindhagen2 , O. Bratt3 , P. Stattin4 , J. Adolfsson5 . 1 King’s College London, Cancer Epidemiology, London, United Kingdom; 2 Uppsala University, Uppsala Clinical Research Centre, Uppsala, Sweden; 3 Lund University, Translational Medicine Urology, Lund, Sweden; 4 Umea University, Surgical and Perioperative SciencesUrology and Andrology, Umea, Sweden; 5 Karolinska Institute, CLINTEC, Stockholm, Sweden Background: Active surveillance (AS) is commonly used for men with low-risk prostate cancer (PCa). When life-expectancy becomes too short for curative treatment to be beneficial, a change from AS to watchful waiting (WW) occurs. Little is known about this transition since it is rarely documented in medical records. The aim of the current study was to assess the change from AS to WW in men with very low-risk PCa. We used a statetransition model to predict what proportion of men changes from AS to WW and when this occurs. Moreover, we investigated how this change from AS to WW is affected by age and comorbidity. Methods: Using population-based data on cancer characteristics, age and comorbidity in PCBaSeTraject , a state-transition model was created
Poster Session, Sunday 29 January 2017 to estimate the probability of treatment changes between pre-defined treatments to predict transitioning from AS to WW. Results: Our predictions indicated that 48% of men with very low-risk PCa starting on AS eventually changed to WW. This proportion increased with age at time of AS initiation. Within ten years from start of AS, 10% of men aged 50 and 50% of men aged 70 with no comorbidity at initiation will transition to WW. The median time on AS was 5 years. Our prevalence simulation suggested that the number of men on WW who were previously on AS only stabilises after 30 years. Conclusions: Changes from AS to WW were predicted to become common in men with very low-risk PCa who were elderly at time of AS initiation. Men remained on AS for a median of five years. The possibility of a change from AS to WW should be part of the treatment pathway discussion with a man considering AS as a treatment option. Clear guidelines on follow-up, including criteria to decide when AS should change to WW and how this should be managed in different healthcare systems, are thus needed. No conflict of interest.
Poster Session (Sunday 29 January 2017) Urology 2169 POSTER Specialties in pathomorphology of moderately differentiated urothelial tumors of upper urinary tract K. Ishchenko1 . 1 Moscow, Moskow Regional Cancer dispanser, Balashiha, Russian Federation This research included morphological analisis of histological preparations of 157 patients with urothelial carcinoma and in 42 cases (26.7%) of wich the modertely differentiated tumor was identified. We conducted a comprehensive morphological research of urothelial cancer of upper urinary tract by using complex of general histological, morphometrical, histochemical and immunohistochemical methods wich allows us making several generalizations. The basic differential morphological features of moderately differentiated urohtelial cancer of renal pelvis are following: – the emptive damage of renal pelvis with prevalence of tumor nodes having papilar character and a presence of sectors with squamous differentiation of tumor cells – moderate cellular and nuclear polymorphism with average indexes of section length of nuclei of tumor cells and nuclear-cytoplasmic ratio are 6.58±0.74 and 0.691±0.083 respectively that grow in the areas of squamous differentiation with increasing the section length of nuclei of tumor cells up to 6.94±0.81 and nuclear-cytoplasmic ratio up to 0.725±0.074; – moderate proliferative activity of cells with indexes of pathological figures of mitosis on average is 8.7‰, mitosis index − 11.6±2.51‰, and the percentage of cells with positive reaction with the specific anti-Ki-67 (antigen of nuclear proliferation), is 46.3±5.9% with the increasing values in sectors of squamous differentiation − 9.1‰, 12.1±2.93‰ and 49.8±6.2% respectively with the invasion of tumor cells into blood vessels, wall of renal pelvis and into ureter, kidney and surrounding cellular tissue; – an uneven distribution and dissemination the sectors of necrosis in tumor tissue with a specific volume of necrois lessions on average is 0.2011±0.0082; – prevalence of intensive anti-tumor immune response with formation of large infiltrations with relatively high indexes of immunocompetent cells in stroma on 1 mm2 (117.18±23.79) and medium number of cells in the one field of view (24.31±4.03), which presented mainly with lymphocytes (83.01±2.62%), macrophages and neutrophils (4.99±0.31%, 4.83±0.21% respectively), with presence of not high number of plasma cells (2.84±0.10%), tissue basophils (1.83±0.17%) and eosinophils (1.80±0.01%). No conflict of interest. 2170 POSTER Induction of VX2 para-renal carcinoma in rabbits: generation of animal model for loco-regional treatments of solid tumors S. Bimonte1 , M. Leongito1 , M. Piccirillo1 , F. Izzo1 . 1 National Cancer Institute Fondazione G. Pascale, Division of Abdominal Surgical Oncology- Hepatobiliary Unit, Naples, Italy Background: Animal models of para-renal cancer can provide useful information for the evaluation of tumor response to loco-regional therapy
Abstracts
group and number of prior VEGFR TKIs (1 or 2). The study was designed to detect a HR for OS of 0.75 (80% power, 2-sided a = 0.04). Results: A total of 658 patients were randomized from Aug 2013 to Nov 2014. As of 31 Dec 2015, with a minimum follow-up of 13 months, 74 (22%) vs 25 (8%) of patients remained on cabo and eve, respectively (Choueiri Lancet Oncol 2016). A total of 320 deaths were recorded (140 for cabo and 180 for eve). The secondary endpoint of improved OS with cabo was met with a p-value of 0.0003, which surpassed the critical boundary of 0.0163 for this analysis. Median OS was significantly prolonged with cabo (21.4 months vs 16.5 months with eve, HR 0.66, 95% CI 0.53–0.83). Landmark estimates of survival at 18 months were 58% in the cabo arm vs 47% in the eve arm. Improvement in OS with cabo was observed in all prespecified subgroups, including MSKCC risk group, number and type of prior VEGFR TKIs, prior anti-PD-1/PD-L1 treatment, location and extent of tumor metastases, and tumor MET expression level. The percent of patients receiving subsequent anticancer therapy was similar in both arms. Safety results were consistent with the previously-reported safety profiles in this population. Conclusions: Significant improvements in OS, PFS, and ORR were observed with cabo in the Phase 3 METEOR trial of previously-treated patients with advanced RCC. Cabo is an important new treatment option for this patient population. Conflict of interest: Ownership: K. Peltola: Faron Pharmaceuticals; D.T. Aftab: Exelixis, Inc.; C. Scheffold: Exelixis, Inc.; G. Schwab: Exelixis, Inc. Advisory Board: R.J. Motzer: Novartis, Exelixis, Eisai, Pfizer; N.M. Tannir: BMS, Exelixis, Nektar, Novartis, Pfizer, Argos, Calithera; P.N. Mainwaring: Astellas, Medication, Janssen Oncology; J.L. Lee: Roche, Astellas; T.E. Hutson: Speakers’ Bureau: Pfizer, Novartis, Bayer, BMS. Corporate-sponsored Research: M. Schmidinger: Pfizer, Roche; R.J. Motzer: Research for clinical trial support to employer (MSKCC), Pfizer, Novartis, Genentech, Roche; T. Powles: Exelixis, Inc., Novartis, GSK, Genentech; N.M. Tannir: BMS, Exelixis, Epizyme, Novartis, Miranti; B.I. Rini: Pfizer, BMS, Accerleron, Immatics, Peleton; H.J. Hammers: sfj, BMS, Exelixis, Newlink, Pfizer, GSK, Tracon; F. Donscov: Novartis, GSK, Pfizer; B. Roth: Exelixis, Inc. (institutional support only); J.L. Lee: Roche, Pfizer, AstraZeneca, Novartis, Johnson and Johnson, BMS; S. Pal: Pfizer, Bayer, BMS; T.E. Hutson: Pfizer, Novartis, Bayer, BMS. Other Substantive Relationships: M. Schmidinger: Honoraria (Pfizer, Roche, BMS, Novartis), Consulting or Advisory Role (Pfizer, Roche, Novartis, BMS, Exelixis); T. Powles: Consulting or Advisory Role (Exelixis, Inc., Novartis, GSK); B. Escudier: Honoraria and Consulting or Advisory Role (Novartis, GSK, Pfizer, Bayer, Exelixis); B.I. Rini: Consulting or Advisory Role (Pfizer, Roche, BMS, Acceleron, Novartis, GSK), Travel, Accomodations, Expenses (Pfizer); H.J. Hammers: Consulting or Advisory Role (BMS, Exelixis, Pfizer, Cerulean); K. Peltola: Employee (Orion Pharma [Part-time]), Honoraria (Lilly, BMS, Sanofi, Pfizer, Novartis), Consulting or Advisory Role (Lilly, BMS, Baxalta, Sanofi, Pfizer, Novartis), Travel, Accomodations, Expenses (BMS, Novartis, Pfizer); D.Y.C. Heng: Consulting or Advisory Role (Pfizer, Novartis, BMS, Exelixis); D.T. Aftab: Employee (Exelixis, Inc.); C. Hessel: Employee (Exelixis, Inc.); G. Schwab: Employee, Officer of the company (Exelixis, Inc.); T.E. Hutson: Honoraria (Pfizer, Novartis, Bayer, BMS), Consulting or Advisory Role (Pfizer, Novartis, Bayer, BMS, Eisai, Exelixis, Inc.); T.K. Choueiri: Consulting or Advisory Role (Pfizer, GSK, Novartis, Merck, Bayer, Eisai, Roche, Prometheus Labs Inc, BMS, Foundation Medicine Inc.). 2118 ORAL Quantifying the transition from active surveillance to watchful waiting in men with very low-risk prostate cancer M. Van Hemelrijck1 , H. Garmo1 , L. Lindhagen2 , O. Bratt3 , P. Stattin4 , J. Adolfsson5 . 1 King’s College London, Cancer Epidemiology, London, United Kingdom; 2 Uppsala University, Uppsala Clinical Research Centre, Uppsala, Sweden; 3 Lund University, Translational Medicine Urology, Lund, Sweden; 4 Umea University, Surgical and Perioperative SciencesUrology and Andrology, Umea, Sweden; 5 Karolinska Institute, CLINTEC, Stockholm, Sweden Background: Active surveillance (AS) is commonly used for men with low-risk prostate cancer (PCa). When life-expectancy becomes too short for curative treatment to be beneficial, a change from AS to watchful waiting (WW) occurs. Little is known about this transition since it is rarely documented in medical records. The aim of the current study was to assess the change from AS to WW in men with very low-risk PCa. We used a statetransition model to predict what proportion of men changes from AS to WW and when this occurs. Moreover, we investigated how this change from AS to WW is affected by age and comorbidity. Methods: Using population-based data on cancer characteristics, age and comorbidity in PCBaSeTraject , a state-transition model was created
Poster Session, Sunday 29 January 2017 to estimate the probability of treatment changes between pre-defined treatments to predict transitioning from AS to WW. Results: Our predictions indicated that 48% of men with very low-risk PCa starting on AS eventually changed to WW. This proportion increased with age at time of AS initiation. Within ten years from start of AS, 10% of men aged 50 and 50% of men aged 70 with no comorbidity at initiation will transition to WW. The median time on AS was 5 years. Our prevalence simulation suggested that the number of men on WW who were previously on AS only stabilises after 30 years. Conclusions: Changes from AS to WW were predicted to become common in men with very low-risk PCa who were elderly at time of AS initiation. Men remained on AS for a median of five years. The possibility of a change from AS to WW should be part of the treatment pathway discussion with a man considering AS as a treatment option. Clear guidelines on follow-up, including criteria to decide when AS should change to WW and how this should be managed in different healthcare systems, are thus needed. No conflict of interest.
Poster Session (Sunday 29 January 2017) Urology 2169 POSTER Specialties in pathomorphology of moderately differentiated urothelial tumors of upper urinary tract K. Ishchenko1 . 1 Moscow, Moskow Regional Cancer dispanser, Balashiha, Russian Federation This research included morphological analisis of histological preparations of 157 patients with urothelial carcinoma and in 42 cases (26.7%) of wich the modertely differentiated tumor was identified. We conducted a comprehensive morphological research of urothelial cancer of upper urinary tract by using complex of general histological, morphometrical, histochemical and immunohistochemical methods wich allows us making several generalizations. The basic differential morphological features of moderately differentiated urohtelial cancer of renal pelvis are following: – the emptive damage of renal pelvis with prevalence of tumor nodes having papilar character and a presence of sectors with squamous differentiation of tumor cells – moderate cellular and nuclear polymorphism with average indexes of section length of nuclei of tumor cells and nuclear-cytoplasmic ratio are 6.58±0.74 and 0.691±0.083 respectively that grow in the areas of squamous differentiation with increasing the section length of nuclei of tumor cells up to 6.94±0.81 and nuclear-cytoplasmic ratio up to 0.725±0.074; – moderate proliferative activity of cells with indexes of pathological figures of mitosis on average is 8.7‰, mitosis index − 11.6±2.51‰, and the percentage of cells with positive reaction with the specific anti-Ki-67 (antigen of nuclear proliferation), is 46.3±5.9% with the increasing values in sectors of squamous differentiation − 9.1‰, 12.1±2.93‰ and 49.8±6.2% respectively with the invasion of tumor cells into blood vessels, wall of renal pelvis and into ureter, kidney and surrounding cellular tissue; – an uneven distribution and dissemination the sectors of necrosis in tumor tissue with a specific volume of necrois lessions on average is 0.2011±0.0082; – prevalence of intensive anti-tumor immune response with formation of large infiltrations with relatively high indexes of immunocompetent cells in stroma on 1 mm2 (117.18±23.79) and medium number of cells in the one field of view (24.31±4.03), which presented mainly with lymphocytes (83.01±2.62%), macrophages and neutrophils (4.99±0.31%, 4.83±0.21% respectively), with presence of not high number of plasma cells (2.84±0.10%), tissue basophils (1.83±0.17%) and eosinophils (1.80±0.01%). No conflict of interest. 2170 POSTER Induction of VX2 para-renal carcinoma in rabbits: generation of animal model for loco-regional treatments of solid tumors S. Bimonte1 , M. Leongito1 , M. Piccirillo1 , F. Izzo1 . 1 National Cancer Institute Fondazione G. Pascale, Division of Abdominal Surgical Oncology- Hepatobiliary Unit, Naples, Italy Background: Animal models of para-renal cancer can provide useful information for the evaluation of tumor response to loco-regional therapy