Annals of Oncology
and Institutional, Other, Consultant: Clovis; Financial Interests, Personal and Institutional, Other,
Consultant: Merck; Financial Interests, Personal and Institutional, Other, Consultant: AstraZeneca;
Financial Interests, Personal and Institutional, Other, Consultant: Myovant; Financial Interests, Per-
sonal and Institutional, Other, Consultant: Exact Sciences; Financial Interests, Personal and Institu-
tional, Invited Speaker: Sanofi; Financial Interests, Personal and Institutional, Invited Speaker:
AstraZeneca.
https://doi.org/10.1016/j.annonc.2021.08.1129
617P Genomic profiling of circulating tumor DNA in advanced
genitourinary cancer patients: SCRUM-Japan MONSTAR
SCREEN Nationwide Cancer Genome Screening Project
T. Kato1, N. Matsubara2, T. Fujisawa3, M. Shiota4, M. Eto5, T. Osawa6, T. Abe6,
N. Shinohara6, Y. Yasumizu7, N. Tanaka7, M. Oya8, K. Nishimoto9, S. Horasawa10,
N. Kuramoto11, Y. Nakamura11, H. Taniguchi11, T. Yoshino12, N. Nonomura1
1
Urology, Graduate School of Medicine / Faculty of Medicine, Osaka University, Suita,
Japan; 2Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa,
Chiba, Japan; 3Department of Head and Neck Medical Oncology, National Cancer
Center Hospital East, Kashiwa, Japan; 4Department of Urology, Graduate School of
Medical Sciences, Kyushu University, Fukuoka, Japan; 5Department of Urology, Kyushu
University Hospital, Fukuoka, Japan; 6Urology, Hokkaido University Graduate School of
Medicine, Sapporo, Japan; 7Urology, Keio University School of Medicine, Tokyo, Japan;
8
Department of Urology, Keio University School of Medicine, Tokyo, Japan; 9Uro-
Oncology, Saitama Medical University International Medical Center, Hidaka, Japan;
10
Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan;
11
Translational Research Support Section, National Cancer Center Hospital East,
Kashiwa, Japan; 12Department of Gastroenterology and Gastrointestinal Oncology,
National Cancer Center Hospital East, Kashiwa, Chiba, Japan
Background: Circulating tumor DNA (ctDNA) is an emerging resource for the diagnosis
and prognosis of various types of cancer. However, characteristics and clinical utility of
ctDNA is still largely unknown, especially in patients with genitourinary (GU) cancers.
Methods: SCRUM-Japan consortium of Nationwide Cancer Genome Screening Project
has started MONSTAR-SCREEN project which evaluates ctDNA for patients with
advanced solid tumors since Apr 2019 in Japan. We collected plasma and tumor
samples in patients with prostate cancer (PC), urothelial carcinoma (UC), and renal
cell carcinoma (RCC). Plasma ctDNA and tumor genomic DNA were analyzed by a
NGS-based ctDNA assay, Foundation OneÒ Liquid (F1L) and tissue-based panel,
Foundation OneÒ CDx (F1CDx), respectively.
Results: As of Sep 2020, 639 patients with advanced solid tumors were enrolled in
MONSTAR-SCREEN. Among them, we analyzed 92 ctDNA samples of advanced GU
cancers (43 PC, 27 UC, and 22 RCC) and compared the feature in GU cancers with that
in non-GU cancers. The level of ctDNA in GU cancers was similar to that in non-GU
cancers (median 1.92% vs. 3.80%, P ¼ 0.229). Although UC possessed the highest
median blood tumor mutation burden (bTMB) in all cancers (4.39), there was no
significant bTMB difference between GU cancers and non-GU cancers (2.63 vs. 2.63, P
¼ 0.995). Interestingly, the mutation rate in genes related to DNA damage response
pathway was significantly higher in GU cancers compared to that in non-GU cancers
(32.6 % vs. 19.7%, P ¼ 0.00879). When we focus on other major oncogenic signaling
pathways such as PI3K, MAPK and Wnt-signal pathway, we found that related genes in
these pathways were less frequently altered in GU cancer versus non-GU cancers (P ¼
0.017, P < 0.001 and P ¼ 0.00327, respectively). We also assessed concordance
between liquid biopsy and tumor tissue-based sequencing and found that two-thirds
of detected variants in F1L were overlapped with that in F1CDx.
Conclusions: For the first time, we performed comprehensive genomic profiling of
ctDNA in GU cancers. We further evaluate ctDNA profiling before and after starting
cancer treatments and connect these data to clinical trials.
Legal entity responsible for the study: SCRUM-Japan MONSTAR-SCREEN.
Funding: Has not received any funding.
Disclosure: All authors have declared no conflicts of interest.
https://doi.org/10.1016/j.annonc.2021.08.1130
Table: 618P
Age, years TITAN, N [ 1052
<65 65-79
n (%) 331 (31.5) 628 (59.7)
Median treatment duration, mo (range) 39.8 (1.0-52.7) 39.8 (0-55.7)
APA vs PBO
Confirmed PSA50,a n (%) 88.6 vs 47.3 90.1 vs 59.2
MFS, HR (95 % CI) NA NA
rPFS, HR (95 % CI) 0.45 (0.31-0.66) 0.51 (0.39-0.68)
OS, HR (95 % CI) 0.57 (0.40-0.80) 0.70 (0.54-0.91)
NA, not applicable. ap < 0.0001 for all comparisons.
S656
abstracts
618P Apalutamide (APA) for advanced prostate cancer in older
patients (pts): Combined analysis of TITAN & SPARTAN
J. Shen1, S. Chowdhury2, N. Agarwal3, L.I. Karsh4, S. Oudard5, B.A. Gartrell6,
S. Feyerabend7, F. Saad8, C.M. Pieczonka9, K.N. Chi10, S.D. Brookman-May11,
B. Rooney12, A. Bhaumik13, A. Londhe14, S.A. McCarthy15, K.B. Bevans16,
S.D. Mundle17, E.J. Small18, M.R. Smith19, J.N. Graff20
1
Department of Gastrointestinal Medical Oncology, Jonsson Comprehensive Cancer
Center, University of California, Los Angeles, CA, USA; 2Division of Cancer Studies,
Guy’s, King’s, and St. Thomas’ Hospitals, and Sarah Cannon Research Institute, Lon-
don, UK; 3Department of Medicine, Huntsman Cancer Institute, University of Utah,
Salt Lake City, UT, USA; 4Department of Research, The Urology Center of Colorado,
Denver, CO, USA; 5Department of Medical Oncology, Georges Pompidou Hospital,
University of Paris, Paris, France; 6Department of Oncology, Montefiore Medical
Center, Bronx, NY, USA; 7Studienpraxis Urologie, Studienpraxis Urologie, Nürtingen,
Germany; 8Division of Medical Oncology, Centre Hospitalier de l’Université de Mon-
tréal, Université de Montréal, Montreal, QC, Canada; 9Department of Oncology,
Associated Medical Professionals of NY, Syracuse, NY, USA; 10Department of Medicine,
BC Cancer and Vancouver Prostate Centre, Vancover, BC, Canada; 11Clinical Research
Oncology, Ludwig-Maximilians-University (LMU), Munich, Germany, Janssen Research
& Development, Los Angeles, CA, USA; 12WC Clinical Oncology, Janssen Research &
Development, High Wycombe, UK; 13US BioStats, Janssen Research & Development,
Titusville, NJ, USA; 14Global BioStats, Janssen Research & Development, Titusville, NJ,
USA; 15Compound Development, Janssen Research & Development, Raritan, NJ, USA;
16
Patient Reported Outcomes, Janssen Research & Development, Horsham, PA, USA;
17
Global Medical Affairs, Janssen Research & Development, Raritan, NJ, USA;
18
Department of Urology, Helen Diller Family Comprehensive Cancer Center, University
of California, San Francisco, CA, USA; 19Urologic Oncology, Massachusetts General
Hospital Cancer Center and Harvard Medical School, Boston, MA, USA; 20Division of
Hematology and Medical Oncology, VA Portland Health Care System and Knight
Cancer Institute, Oregon Health & Science University, Portland, OR, USA
Background: In TITAN and SPARTAN, APA added to continuous androgen deprivation
therapy (ADT) improved prostate-specific antigen (PSA) response, radiographic pro-
gression-free survival (rPFS), metastasis-free survival (MFS), and overall survival (OS)
in pts with metastatic castration-sensitive prostate cancer (mCSPC) and nonmetastatic
castration-resistant prostate cancer (nmCRPC). We assessed efficacy and safety of APA
in age groups from both studies.
Methods: mCSPC and nmCRPC pts were randomized 1:1 and 2:1 to receive APA (240
mg QD) or PBO plus ADT, and PBO-to-APA crossover after first interim analysis (IA1)
was 39.5% and 19%, respectively. In this post hoc analysis, pts were stratified by age
< 65, 65-79, and  80 y. Time-to-event end points were analyzed by Kaplan-Meier
method and Cox proportional hazards model: rPFS and MFS at IA1 (TITAN: 22.7 mo,
SPARTAN: 20.3 mo median follow-up); PSA  50% decrease from baseline (PSA50),
OS, and health-related quality of life (HRQoL) per Functional Assessment of Cancer
Therapy-Prostate were analyzed at final analysis (TITAN: 44 mo, SPARTAN: 52 mo
median follow-up).
Results: 1052 mCSPC (525 APA, 527 PBO), and 1207 nmCRPC (806 APA, 401 PBO) pts
were assessed. APA added to ADT improved: PSA50 in all age groups, primary end
points in all age groups but 80 y TITAN pts, and OS in < 65 and 65-79 y groups in
TITAN and < 65 y group in SPARTAN (Table). HRQoL was maintained regardless of age
or treatment group, with low side effect burden. In both studies, exposure-adjusted
rates of adverse events (AEs) leading to treatment discontinuation, falls, and ischemic
heart disease were increased with age regardless of treatment, and rates of skin rash
were increased with age in the APA groups.
Conclusions: Patients with mCSPC and nmCRPC derived clinical benefit and main-
tained HRQoL from APA plus ADT, but oldest pts had a trend toward less benefit with
increasing age, increased AE rates, and shorter treatment duration.
Clinical trial identification: NCT02489318, NCT01946204.
Editorial acknowledgement: Writing assistance was provided by Larissa Belova, PhD,
of Parexel, and was funded by Janssen Global Services, LLC.
Legal entity responsible for the study: Janssen Research & Development, LLC.
Funding: Janssen Research & Development.
Disclosure: J. Shen: Other, Personal, Advisory Board: AstraZeneca; Other, Institutional, Research
Grant: Merck; Other, Institutional, Research Grant: BMS; Other, Institutional, Research Grant:
SPARTAN, N [ 1207
80 <65 65-79 80
93 (8.8) 149 (12.3) 741 (61.4) 317 (26.3)
23.6 (2.0-48.2) 46.2 (0.5-69.8) 33.4 (0.3-74.5) 20.6 (0.1-73.3)
94.2 vs 58.5 92.5 vs 2.3 91.7 vs 2.0 84.1 vs 2.8
NA 0.14 (0.08-0.27) 0.29 (0.23-0.37) 0.43 (0.28-0.65)
0.55 (0.25-1.21) NA NA NA
0.74 (0.40-1.39) 0.39 (0.19-0.78) 0.89 (0.69-1.16) 0.81 (0.58-1.15)
Volume 32 - Issue S5 - 2021