- Email: [email protected]
metastatic gall bladder cancer (GBC) patients with ECOG PS-III. Results from a phase II randomised controlled trial (RCT)
abstracts
Annals of Oncology
725P
Capecitabine 1best supportive care (BSC) or erlotinib 1BSC has overall survival (OS) benefit over BSC alone in unresectable/metastatic gall bladder cancer (GBC) patients with ECOG PS-III. Results from a phase II randomised controlled trial (RCT)
Background: Gemcitabine with platinum is regarded as the standard of care in patients with unresectable and/or metastatic disease with good performance status (PS). There is no standard of care for poor PS patients. A report from M.D.A.C.C. stated a median OS of only one month in GBC patients with poor PS. Erlotinib and capecitabine, both have shown efficacy in metastatic GBC. There has been no RCT to date in GBC patients with poor PS. With limited data showing the activity of erlotinib and capecitabine, we conducted this RCT to evaluate the efficacy and toxicity of these drugs in this patient cohort. Methods: This is an ongoing open-label, phase II/III RCT (phase II part of the study is complete).The primary objective is to determine if erlotinib (150 mg/d PO )þ BSC or capecitabine (625 mg/m2 BD PO) þ BSC has an OS benefit compared to BSC alone in patients with unresectable/metastatic GBC with ECOG PS III. A total of 51 patients with histopathologically confirmed GBC, age >/¼18 years, with adequate organ functions (S. bilirubin < ¼ 3.5 g/dl, AST/ALT within 5 times the normal limit and eGFR > 50 ml/min/1.73m2) were randomised. Patients were followed up q2wk in first month and q4wk thereafter. Toxicity was assessed using CTCAE v4.1. Radiological response evaluation (as per RECIST v1.1) was done at 8-10 weeks/earlier if clinically indicated, QoL assessment (using EORTC QLQ-C30 BIL21 ) was done at baseline and at 6-8 weeks. Intervention was continued until progression/unacceptable toxicity. Serial evaluation for OS in all three arms was done. Initially the study was started as a phase II RCT, an interim pre-planned analysis was done after completion of phase II. Results: The median OS in capecitabine þBSC arm (n ¼ 19) was 209 days, relotinib þBSC arm(n ¼ 14) was 105 days and BSC alone arm was 71 days (p value 0.022). Only 2 patients had grade III diarrhea with erlotinib. There were no drug-related SAEs. Conclusions: There is a statistically significant OS benefit of capecitabineþBSC or erlotinibþBSC over BSC alone in unresectable/metastatic GBC patients with ECOG PS III. Results will be updated upon completion of phase III. Clinical trial identification: CTRI/2019/04/018860. Legal entity responsible for the study: The authors. Funding: All India Institute of Academic Sciences. Disclosure: All authors have declared no conflicts of interest.
726P
FGFR2 fusions and its effect of patient (pt) outcomes in intrahepatic cholangiocarcinoma (iCCA)
D.R. Almquist1, M. Javle2, K.K. Ciombor3, M. Roth3, R. Abdel-Wahab2, F-S. Ou4, E. Wolfe5, K. Mody6, A. Mahipal7, M.J. Borad8, T. Bekaii-Saab9, D. Ahn10 1 Oncology, Mayo Clinic Cancer Center, Phoenix, AZ, USA, 2Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA3Medical Center, Vanderbilt University, Nashville, TN, USA, 4Biostatistics, Mayo Clinic, Scottsdale, AZ, USA, 5Health Sciences Research, Mayo Clinic, Rochester, MN, USA, 6Oncology, Mayo Clinic, Jacksonville, FL, USA, 7Medical Oncology, Mayo Clinic, Rochester, MN, USA, 8Medical Oncology, Mayo Clinic Cancer Center, Scottsdale, AZ, USA, 9Medical Oncology, Mayo Clinic Cancer Center, Phoenix, AZ, USA, 10Hematology/Medical Oncology, Mayo Clinic Cancer Center, Phoenix, AZ, USA Background: iCCA is a genomically diverse disease where various genomic alterations have been identified. FGFR2 fusions are present in up to 15% of iCCA tumors and are drivers that result in activation of the FGFR pathway. While early studies implicate their potential as a therapeutic target, thier impact on the natural course of the disease is unknown. Herein, we describe the natural history iCCA FGFR2 fusions, its prognostic role and utility for FGFR-targeted therapy. Methods: A multi-center, retrospective analysis was performed, where we identified pts with advanced iCCA. FGFR2 fusions were detected by using a CLIA certified next generation sequencing panel or fluorescence in situ hybridization. We assessed pt outcomes with advanced iCCA whose tumors were identified as having FGFR2 fusions compared to those that did not exhibit FGFR2 fusions. Univariate Cox regression model was used to determine the association between gene alterations with progression free survival (PFS) and (OS). Results: One hundred thirty-five pts with advanced iCCA were identified, with fortyfive having FGFR2 fusions. In patients with iCCA, FGF2R fusions appeared to occur at a younger age (55 v 58 yrs; p ¼ 0.1919) compared to the control but was not signficant. Ethnicity (p ¼ 0.5162), gender (p ¼ 0.4967), differentiation (p ¼ 0.7754) were
Volume 30 | Supplement 5 | October 2019
727P
The clinical outcomes of systemic chemotherapy in patients with unresectable or metastatic combined hepatocellularcholangiocarcinoma (HCC-CCA): Retrospective study of 120 patients
E. Kim1, C. Yoo2, B-Y. Ryoo2 Internal Medicine, Asan Medical Center, Seoul, Republic of Korea, 2Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
1
Background: Combined HCC-CCA is rare malignancy with incidence of less than 5% of primary hepatic malignancies. Because combined HCC-CCA has been excluded in clinical trials for either HCC or CCA, optimal systemic chemotherapy regimen has not been defined yet for combined HCC-CCA. Therefore, we analyzed efficacy of systemic chemotherapy in patients with unresectable or metastatic combined HCC-CCA. Methods: Among patients with histologically confirmed combined HCC-CCA from 1999 to 2015 in Asan Medical Center, Seoul, Korea, 120 patients who received systemic chemotherapy for unresectable or metastatic disease were identified and included in this analysis. Overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were retrospectively evaluated. Results: 15 patients had initially metastatic disease and the other 105 patients had recurrent or progressive disease after local therapy. Sorafenib (n ¼ 69, 56.7%), gemcitabine plus cisplatin (GP) (n ¼ 21, 17.5%), 5-FU-based chemotherapy (n ¼ 22, 19.2%) were most frequently used regimens. Overall, ORR was 10.8%, and median PFS and OS was 4.2 (95% CI 3.0-5.5) and 9.0 months (7.0-11.1), respectively with median followup of 39.6 months (24.8-54.3). ORR, PFS and OS did not differ according to chemotherapy regimens (ORR, 7.2%, 13.7% and 18.2%, p ¼ 0.30; median PFS, 4.6 [95% CI 3.8-5.4], 3.7 [1.8-5.6] and 7.9 months [0.5-15.2], p ¼ 0.67; and median OS, 9.8 [7.512.1], 8.8 [6.8-10.8], and 8.8 months [4.9-12.7], p ¼ 0.62 in patients with sorafenib, GP, and 5-FU-based chemotherapy, respectively). In univariate analysis, elevated baseline carcinoembryonic antigen (CEA) level, liver cirrhosis (LC) and large tumor burden (30% of liver volume) were significantly associated with poorer OS, and these remained significant in multivariate analysis (HR 2.29, 95% CI, 1.26-4.14, p ¼ 0.006 for elevated CEA level; HR 1.67, 1.03-2.70, p ¼ 0.04 for LC; HR 4.75, 2.22-10.16, p < 0.001 for large tumour burden). Conclusions: Patients with advanced HCC-CCA treated with systemic chemotherapy showed poor prognosis. Further clinical trials to understand biology of combined HCC-CCA and find optimal systemic agents are needed. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
728P
High PD-L1 expression is associated with treatment response to pembrolizumab in patients with advanced biliary tract cancer
G. Kim1, S. Ahn1, J-H. Hwang2, J-C. Lee2, J. Kim2 Pathology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea, 2 Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
1
Background: Pembrolizumab has shown promising results for patients with programmed cell death ligand-1 (PD-L1)-positive solid tumors. However, data on immunotherapy for biliary tract cancers are limited, and biomarkers to identify appropriate candidates for immunotherapy needs to be defined. Methods: A total of 153 patients with advanced biliary tract cancers were included (gallbladder n ¼ 48, distal bile duct n ¼ 17, perihilar bile duct n ¼ 32, intrahepatic bile duct n ¼ 49, and ampulla of vater n ¼ 7). Patients were screened for PD-L1 expression by a prototype immunohistochemistry assay (PharmDx). Of PD-L1-positive patients, 12 patients were treated with pembrolizumab. Treatment response was evaluated and correlated with PD-L1 immunohistochemistry, microsatellite instability (MSI) status, tumor-infiltrating lymphocytes (TIL), and CD8þ T cells density.
doi:10.1093/annonc/mdz247 | v279
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz247.052/5576576 by guest on 24 October 2019
B. Kataria1, A. Sharma2, S. Mishra1, S. Bhatnagar1, S. Thulkar3, M. Yadav4, R.K. Sahoo5, R. Pramanik1, C.P. Prasad6, V. Sreenivas7, M.K. S8 1 Medical Oncology, Dr.,B.R.A.I.R.C.H.,AIIMS - All India Institute of Medical Sciences, New Delhi, India, 2Medical Oncology, B.R. Ambedkar Institute Rotary Cancer Hospital (AIMS), New Delhi, India, 3Radiology, B.R. Ambedkar Institute Rotary Cancer Hospital (AIMS), New Delhi, India, 4Radiology, Dr.,B.R.A.I.R.C.H.,AIIMS - All India Institute of Medical Sciences, New Delhi, India, 5Medical Oncology, B.R. Ambedkar Institute Rotary Cancer Hospital (AIIMS), New Delhi, India, 6Medical Oncology (Lab), AIIMS - All India Institute of Medical Sciences, New Delhi, India, 7Biostatistics, B.R. Ambedkar Institute Rotary Cancer Hospital (AIMS), New Delhi, India, 8Radiology, AIIMS - All India Institute of Medical Sciences, New Delhi, India
evaluated and were not significantly different between groups iCCA FGFR2 fusions pts were more likely to be diagnosed with advanced disease, stage IIIB or greater (p ¼ 0.0016). No significant differences in PFS were observed from gemcitabine-platinum based chemotherapy in pts whose tumors exhibited FGFR2 fusions (0.5 v 0.5 yrs, HR 1.19, P ¼ 0.36). An significant median OS was observed in pts whose tumors exhibited FGFR2 fusions compared to those that were WT for FGFR2 fusions (2.7 vs 1.3 yrs, HR 0.44, p ¼ 0.002). Conclusions: Somatic FGFR2 fusions were associated with a significant survival advantage in pts with advanced iCCA. FGFR2 fusions may also be prognostic to chemotherapy response. FGFR is a therapeutic target of interest, where future prospective studies will be necessary to validate the predictive, prognostic utility and its relevance in pt outcomes in iCCA. Legal entity responsible for the study: Daniel Ahn. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Annals of Oncology
725P
Capecitabine 1best supportive care (BSC) or erlotinib 1BSC has overall survival (OS) benefit over BSC alone in unresectable/metastatic gall bladder cancer (GBC) patients with ECOG PS-III. Results from a phase II randomised controlled trial (RCT)
Background: Gemcitabine with platinum is regarded as the standard of care in patients with unresectable and/or metastatic disease with good performance status (PS). There is no standard of care for poor PS patients. A report from M.D.A.C.C. stated a median OS of only one month in GBC patients with poor PS. Erlotinib and capecitabine, both have shown efficacy in metastatic GBC. There has been no RCT to date in GBC patients with poor PS. With limited data showing the activity of erlotinib and capecitabine, we conducted this RCT to evaluate the efficacy and toxicity of these drugs in this patient cohort. Methods: This is an ongoing open-label, phase II/III RCT (phase II part of the study is complete).The primary objective is to determine if erlotinib (150 mg/d PO )þ BSC or capecitabine (625 mg/m2 BD PO) þ BSC has an OS benefit compared to BSC alone in patients with unresectable/metastatic GBC with ECOG PS III. A total of 51 patients with histopathologically confirmed GBC, age >/¼18 years, with adequate organ functions (S. bilirubin < ¼ 3.5 g/dl, AST/ALT within 5 times the normal limit and eGFR > 50 ml/min/1.73m2) were randomised. Patients were followed up q2wk in first month and q4wk thereafter. Toxicity was assessed using CTCAE v4.1. Radiological response evaluation (as per RECIST v1.1) was done at 8-10 weeks/earlier if clinically indicated, QoL assessment (using EORTC QLQ-C30 BIL21 ) was done at baseline and at 6-8 weeks. Intervention was continued until progression/unacceptable toxicity. Serial evaluation for OS in all three arms was done. Initially the study was started as a phase II RCT, an interim pre-planned analysis was done after completion of phase II. Results: The median OS in capecitabine þBSC arm (n ¼ 19) was 209 days, relotinib þBSC arm(n ¼ 14) was 105 days and BSC alone arm was 71 days (p value 0.022). Only 2 patients had grade III diarrhea with erlotinib. There were no drug-related SAEs. Conclusions: There is a statistically significant OS benefit of capecitabineþBSC or erlotinibþBSC over BSC alone in unresectable/metastatic GBC patients with ECOG PS III. Results will be updated upon completion of phase III. Clinical trial identification: CTRI/2019/04/018860. Legal entity responsible for the study: The authors. Funding: All India Institute of Academic Sciences. Disclosure: All authors have declared no conflicts of interest.
726P
FGFR2 fusions and its effect of patient (pt) outcomes in intrahepatic cholangiocarcinoma (iCCA)
D.R. Almquist1, M. Javle2, K.K. Ciombor3, M. Roth3, R. Abdel-Wahab2, F-S. Ou4, E. Wolfe5, K. Mody6, A. Mahipal7, M.J. Borad8, T. Bekaii-Saab9, D. Ahn10 1 Oncology, Mayo Clinic Cancer Center, Phoenix, AZ, USA, 2Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA3Medical Center, Vanderbilt University, Nashville, TN, USA, 4Biostatistics, Mayo Clinic, Scottsdale, AZ, USA, 5Health Sciences Research, Mayo Clinic, Rochester, MN, USA, 6Oncology, Mayo Clinic, Jacksonville, FL, USA, 7Medical Oncology, Mayo Clinic, Rochester, MN, USA, 8Medical Oncology, Mayo Clinic Cancer Center, Scottsdale, AZ, USA, 9Medical Oncology, Mayo Clinic Cancer Center, Phoenix, AZ, USA, 10Hematology/Medical Oncology, Mayo Clinic Cancer Center, Phoenix, AZ, USA Background: iCCA is a genomically diverse disease where various genomic alterations have been identified. FGFR2 fusions are present in up to 15% of iCCA tumors and are drivers that result in activation of the FGFR pathway. While early studies implicate their potential as a therapeutic target, thier impact on the natural course of the disease is unknown. Herein, we describe the natural history iCCA FGFR2 fusions, its prognostic role and utility for FGFR-targeted therapy. Methods: A multi-center, retrospective analysis was performed, where we identified pts with advanced iCCA. FGFR2 fusions were detected by using a CLIA certified next generation sequencing panel or fluorescence in situ hybridization. We assessed pt outcomes with advanced iCCA whose tumors were identified as having FGFR2 fusions compared to those that did not exhibit FGFR2 fusions. Univariate Cox regression model was used to determine the association between gene alterations with progression free survival (PFS) and (OS). Results: One hundred thirty-five pts with advanced iCCA were identified, with fortyfive having FGFR2 fusions. In patients with iCCA, FGF2R fusions appeared to occur at a younger age (55 v 58 yrs; p ¼ 0.1919) compared to the control but was not signficant. Ethnicity (p ¼ 0.5162), gender (p ¼ 0.4967), differentiation (p ¼ 0.7754) were
Volume 30 | Supplement 5 | October 2019
727P
The clinical outcomes of systemic chemotherapy in patients with unresectable or metastatic combined hepatocellularcholangiocarcinoma (HCC-CCA): Retrospective study of 120 patients
E. Kim1, C. Yoo2, B-Y. Ryoo2 Internal Medicine, Asan Medical Center, Seoul, Republic of Korea, 2Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
1
Background: Combined HCC-CCA is rare malignancy with incidence of less than 5% of primary hepatic malignancies. Because combined HCC-CCA has been excluded in clinical trials for either HCC or CCA, optimal systemic chemotherapy regimen has not been defined yet for combined HCC-CCA. Therefore, we analyzed efficacy of systemic chemotherapy in patients with unresectable or metastatic combined HCC-CCA. Methods: Among patients with histologically confirmed combined HCC-CCA from 1999 to 2015 in Asan Medical Center, Seoul, Korea, 120 patients who received systemic chemotherapy for unresectable or metastatic disease were identified and included in this analysis. Overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were retrospectively evaluated. Results: 15 patients had initially metastatic disease and the other 105 patients had recurrent or progressive disease after local therapy. Sorafenib (n ¼ 69, 56.7%), gemcitabine plus cisplatin (GP) (n ¼ 21, 17.5%), 5-FU-based chemotherapy (n ¼ 22, 19.2%) were most frequently used regimens. Overall, ORR was 10.8%, and median PFS and OS was 4.2 (95% CI 3.0-5.5) and 9.0 months (7.0-11.1), respectively with median followup of 39.6 months (24.8-54.3). ORR, PFS and OS did not differ according to chemotherapy regimens (ORR, 7.2%, 13.7% and 18.2%, p ¼ 0.30; median PFS, 4.6 [95% CI 3.8-5.4], 3.7 [1.8-5.6] and 7.9 months [0.5-15.2], p ¼ 0.67; and median OS, 9.8 [7.512.1], 8.8 [6.8-10.8], and 8.8 months [4.9-12.7], p ¼ 0.62 in patients with sorafenib, GP, and 5-FU-based chemotherapy, respectively). In univariate analysis, elevated baseline carcinoembryonic antigen (CEA) level, liver cirrhosis (LC) and large tumor burden (30% of liver volume) were significantly associated with poorer OS, and these remained significant in multivariate analysis (HR 2.29, 95% CI, 1.26-4.14, p ¼ 0.006 for elevated CEA level; HR 1.67, 1.03-2.70, p ¼ 0.04 for LC; HR 4.75, 2.22-10.16, p < 0.001 for large tumour burden). Conclusions: Patients with advanced HCC-CCA treated with systemic chemotherapy showed poor prognosis. Further clinical trials to understand biology of combined HCC-CCA and find optimal systemic agents are needed. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
728P
High PD-L1 expression is associated with treatment response to pembrolizumab in patients with advanced biliary tract cancer
G. Kim1, S. Ahn1, J-H. Hwang2, J-C. Lee2, J. Kim2 Pathology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea, 2 Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
1
Background: Pembrolizumab has shown promising results for patients with programmed cell death ligand-1 (PD-L1)-positive solid tumors. However, data on immunotherapy for biliary tract cancers are limited, and biomarkers to identify appropriate candidates for immunotherapy needs to be defined. Methods: A total of 153 patients with advanced biliary tract cancers were included (gallbladder n ¼ 48, distal bile duct n ¼ 17, perihilar bile duct n ¼ 32, intrahepatic bile duct n ¼ 49, and ampulla of vater n ¼ 7). Patients were screened for PD-L1 expression by a prototype immunohistochemistry assay (PharmDx). Of PD-L1-positive patients, 12 patients were treated with pembrolizumab. Treatment response was evaluated and correlated with PD-L1 immunohistochemistry, microsatellite instability (MSI) status, tumor-infiltrating lymphocytes (TIL), and CD8þ T cells density.
doi:10.1093/annonc/mdz247 | v279
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz247.052/5576576 by guest on 24 October 2019
B. Kataria1, A. Sharma2, S. Mishra1, S. Bhatnagar1, S. Thulkar3, M. Yadav4, R.K. Sahoo5, R. Pramanik1, C.P. Prasad6, V. Sreenivas7, M.K. S8 1 Medical Oncology, Dr.,B.R.A.I.R.C.H.,AIIMS - All India Institute of Medical Sciences, New Delhi, India, 2Medical Oncology, B.R. Ambedkar Institute Rotary Cancer Hospital (AIMS), New Delhi, India, 3Radiology, B.R. Ambedkar Institute Rotary Cancer Hospital (AIMS), New Delhi, India, 4Radiology, Dr.,B.R.A.I.R.C.H.,AIIMS - All India Institute of Medical Sciences, New Delhi, India, 5Medical Oncology, B.R. Ambedkar Institute Rotary Cancer Hospital (AIIMS), New Delhi, India, 6Medical Oncology (Lab), AIIMS - All India Institute of Medical Sciences, New Delhi, India, 7Biostatistics, B.R. Ambedkar Institute Rotary Cancer Hospital (AIMS), New Delhi, India, 8Radiology, AIIMS - All India Institute of Medical Sciences, New Delhi, India
evaluated and were not significantly different between groups iCCA FGFR2 fusions pts were more likely to be diagnosed with advanced disease, stage IIIB or greater (p ¼ 0.0016). No significant differences in PFS were observed from gemcitabine-platinum based chemotherapy in pts whose tumors exhibited FGFR2 fusions (0.5 v 0.5 yrs, HR 1.19, P ¼ 0.36). An significant median OS was observed in pts whose tumors exhibited FGFR2 fusions compared to those that were WT for FGFR2 fusions (2.7 vs 1.3 yrs, HR 0.44, p ¼ 0.002). Conclusions: Somatic FGFR2 fusions were associated with a significant survival advantage in pts with advanced iCCA. FGFR2 fusions may also be prognostic to chemotherapy response. FGFR is a therapeutic target of interest, where future prospective studies will be necessary to validate the predictive, prognostic utility and its relevance in pt outcomes in iCCA. Legal entity responsible for the study: Daniel Ahn. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.