Startseite Kongressberichte 2019 Annual Meeting of the American Society of Clinical Oncology 2019 Urogenital Cancers Poster Presentations

Choice of Poster Presentations

Prostate Cancer

Christopher Sweeney, Ivor John Percent, Sunil Babu, Jennifer Cultrera, et al.

Phase 1b/2 study of enzalutamide (ENZ) with LY3023414 (LY) or placebo (PL) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) after progression on abiraterone.

Conclusions: Combination LY+ENZ had a clinically manageable safety profile. The primary end-point of PCWG2-PFS was met and is supported by a clinically meaningful delay in rPFS in AR-V7 negative pts. The biomarker data provide important insights to inform future development strategies. Clinical trial information: NCT02407054

  LY+ENZ
N=65a		 PL+ENZ
N=64a		 Unstratified HR
(95% CI), P-value
rPFS, median (mos) 7.5 5.3 0.68 (0.41, 1.14), 0.069
rPFS AR-V7 negative, median (mos) 13.2 (n=51) 5.3 (n=54) 0.52 (0.28, 0.95), 0.028
rPFS AR-V7 positive, median (mos) 5.5 (n=9) 3.6 (n=8) 0.99 (0.27, 3.63), 0.991
>50% reduction in PSA, % 20 25  
Adverse event (AE), All / Grade ≥3, % 98 / 48 98 / 42  
Discontinuation due to AE, % 20 6  
Fatigue b 29 / 23 / 11 28 / 20 / 3  
Nausea b 23 / 28 / 8 20 / 11 / 2  
Diarrhea b 28 / 23 / 6 8 / 6 / 2  

a Number of pts, unless stated otherwise b Treatment-emergent AEs in >30% of all pts, Grade 1 / 2 / ≥3, %

 

Peter C.C. Fong, Margitta Retz, Alexandra Drakaki, Christophe Massard, et al.

Pembrolizumab (pembro) plus enzalutamide (enza) in abiraterone (abi)-pretreated patients (pts) with metastatic castrate resistant prostate cancer (mCRPC): Cohort C of the phase 1b/2 KEYNOTE-365 study.

 

Conclusions: The pembro + enza combination showed sustained activity in abi-pretreated chemotherapy-naive mCRPC. AEs were considered tolerable for the treatment combination; incidence of rash resolved with standard-of-care treatment. Clinical trial information: NCT02861573

PSA response, n/N (%)  
Total population 18/67 (27)
Measurable disease 10/25 (40)
ORR, per RECSIT v1.1 pts w/measurable disease, n/N (%) 5/25 (20); 2 CR, 3 PR
DCR per RECIST v1.1, n/N (%)  
Total population 23/69 (33)
Measurable disease 8/25 (32)
Duration of response per RECIST v1.1, median (range), mo 8.3 (0.0+ to 13.0+)
DOR, ≥6 mo, n (%) 3 (75)
Time to confirmed PSA progression in pts with measurable disease, median (95% CI), wk 18 (15-48)
No confirmed PSA progression at 27 wk in pts with measurable disease, % 50
rPFS, PCWG-modified RECIST, median (95% CI), mo 6 (4-8)
OS, median (95% CI), mo Not reached (12 to not reached)

 

Xiangnan Guan, Duan-Chen Sun, Eric Lu, Joshua A. Urrutia, et al.
Conclusions: Copy number loss of specific tumor suppressor genes is associated with enza resistance in mCRPC patients. Previously unappreciated molecular subsets of enza-resistant CRPC were identified, including one subset associated with poor clinical outcome.
 
 
Michael J. Morris, Jeremy C. Durack, Ajjai Shivaram Alva, Hebert Alberto Vargas, et al.

Conclusions:18F-DCFPyL PET/CT was well tolerated and demonstrated high sensitivity and PPV in accurately detecting nodal, bone, and visceral/soft tissue metastases. A positive 18F-DCFPyL PET/CT scan is highly likely to represent pathologically proven distant disease, demonstrating the potential of 18F-DCFPyL as a PET imaging agent to favorably influence treatment planning. Clinical trial information: NCT02981368

Anatomic Location N Evaluable Sensitivity PPV
Range for 3 readers (%)
(lower bound of 95% CI (%))		 Range for 3 readers (%)
(lower bound of 95% CI (%))
All tissues 92-93 92.9-98.6 (84.0-91.6) 81.2-87.8 (72.9-80.0)
Bone 43-44 90.3-96.9 (74.0-82.9) 78.9-82.3 (66.0-69.5)
Lymph Node 39 93.3-100 (77.6-86.0) 80.0-90.6 (66.8-75.0)
Viscera/Soft Tissue 10 88.9-100 (54.0-65.5) 90.0-100 (57.0-62.0)

 

Panagiotis J. Vlachostergios, Muhammad Junaid Niaz, Seyed Ali Mosallaie, Paul J. Christos, et al.
Conclusions: This is the first study to formally analyze response to PSMA-TRT by PSMA imaging expression in an unselected patient population. The level of PSMA expression measured by imaging is associated with the chance of response. However, a subset of patients without any significant PSMA uptake on imaging did demonstrate response to PSMA-TRT, indicating that imaging cannot exclude all patients that might benefit. Clinical trial information: NCT03545165, NCT03276572, NCT03042468, NCT02552394,
 
 
Jeremie Calais, Francesco Ceci, Matthias Eiber, Tore Bach-Gansmo, et al.
Conclusions: In patients with BCR and low serum PSA levels after RP, PSMA PET/CT demonstrates higher detection rates and superior reader agreement when compared with FACBC PET/CT. Therefore, PSMA PET/CT should be the imaging modality of choice in patients with early BCR. Clinical trial information: NCT03515577
 
 
David Margel, Avivit Peer, Yaara Ber, Sivan Sela, et al.
 
Conclusions: This is the first prospective study to test cardiovascular outcome among prostate-cancer patients receiving ADT. We demonstrated that in patients with pre-existing CVD, GnRH-antagonists was associated with development of fewer cardiovascular events compared to GnRH-agonists. Clinical trial information: NCT02475057
 
Catherine Handy Marshall, Wei Fu, Hao Wang, Bruce J. Trock, et al.

Conclusions: Deferred ADT in relapsing M0 patients is associated with long OS measured from time of local treatment, comparable to OS with salvage ADT in contemporary experience. Drug approval trials in nmCRPC should focus on patients at high risk for metastasis and death prior to ADT, and determine standardized criteria for initiation of ADT. Prolongation of MFS in nmCRPC requires further validation and may not necessarily reflect a net OS benefit.

  Overall PSADT < = 6 months PSADT < = 10 months
# who develop mets 489 (29%) 172 (61%) 260 (55%)
Median MFS, yrs (95% CI) 21 (20-24) 9 (8-10) 12 (10-13)
Median OS, yrs (95% CI) 22 (21-23) 13 (11-15) 15 (13-18)

 

Giulia Baciarello, Remy Delva, Gwenaelle Gravis, Youssef Tazi, et al.
Conclusions: Although cabazitaxel and docetaxel have similar efficacy when used as first-line in mCRPC men, more patients prefer cabazitaxel. Clinical trial information: NCT02044354
 
 

Metastatic Renal Cell Carcinoma (MRCC)

Brian I. Rini, Robert J. Motzer, Thomas Powles, David F. McDermott, et al.

Atezolizumab (atezo) + bevacizumab (bev) versus sunitinib (sun) in pts with untreated metastatic renal cell carcinoma (mRCC) and sarcomatoid (sarc) histology: IMmotion151 subgroup analysis.

 

Conclusions: mRCC pts with sarc histology had longer OS and PFS and a higher ORR/CR rate when treated with atezo + bev vs sun, regardless of PD-L1 status. Biomarker data support a biological correlate for the increased responsiveness to atezo + bev in sarc pts. Clinical trial information: NCT02420821

  All Sarc
 PD-L1+ Sarc
Atezo + Bev
n = 68		 Sun
n = 74		 Stratified HR Atezo + Bev
n = 36		 Sun
n = 50		 Stratified HR
mPFS, mo 8.3 5.3 0.52 8.6 5.6 0.45
  (5.4, 12.9) (3.3, 6.7) (0.34, 0.79) (3.9, 15.3) (3.3, 6.7) (0.26, 0.77)
mOS, mo NR 15.0 0.56 NR 15.0 0.53
  (18.3, NR) (8.7, NR) (0.32, 0.96) (17.1, NR) (8.4, NR) (0.27, 1.06)
12-mo OS, % 69 60 — 71 61 —
  (58, 81) (48, 71)   (56, 86) (47, 75)  
ORR, % 49 14 — 56 12 —
  (36, 61) (7, 23)   (38, 72) (5, 24)  
CR, % 10 3 — 14 4 —
TTD MDASI, mo 11.3 4.9 0.61 — — —
  (6.3, 17.5) (3.5, 7.6) (0.33, 1.11)      

m, median NR, not reached Parentheses denote 95% CI Stratification factors: MSKCC risk score, liver mets, PD-L1 status

 

David F. McDermott, Toni K. Choueiri, Robert J. Motzer, Osvaldo Rudy Aren, et al.

CheckMate 214 post-hoc analyses of nivolumab plus ipilimumab or sunitinib in IMDC intermediate/poor-risk patients with previously untreated advanced renal cell carcinoma with sarcomatoid features.

Conclusions: In this post-hoc descriptive subgroup analysis of CheckMate 214, N+I demonstrated promising efficacy and prolonged survival vs S, with consistent safety, in previously untreated, I/P-risk, advanced clear-cell RCC with sarcomatoid features. Prospective studies of N+I that include pts with sRCC are ongoing. Clinical trial information: NCT02231749

  Randomized I/P-risk sRCC pts Randomized I/P-risk sRCC pts P value/HR (95% CI)
N+I (N = 60) S (N = 52)  
ORR, % (95% CI) 56.7 (43.2–69.4) 19.2 (9.6–32.5) P< 0.001
Complete response, % 18.3 0 –
Median PFS, mo 8.4 (5.2–24.0) 4.9 (4.0–7.0) HR (95% CI), 0.61 (0.38‒0.97); P< 0.03
Median OS, mo 31.2 (23.0‒NE) 13.6 (7.7‒20.9) HR (95% CI), 0.55 (0.33‒0.90); P< 0.0155
NE, not estimable      

Ziad Bakouny, Natalie Vokes, Xin Gao, Amin Nassar, et al.

Conclusions: Pts with S/R mRCC have a higher frequency of BAP1 GA and better outcomes on ICIs compared to non-ICI-based therapies. Future studies should determine the molecular mechanisms underlying the improved response to ICIs in S/R mRCC.
  ICI
(N = 39)		 Non-ICI
(N = 86; 90.7% TKI-based)		 Univariable
(OR/HR)		 Multivariable*
(adjusted OR/HR)
ORR
(N = 109)		 16/37 (43.2%) 20/72 (27.8%) 1.98 (0.86 – 4.54) 3.02 (1.15 – 7.98)
Median TTF
(111/125 events)		 4.8 m (1.6 – 8.0) 4.9 m (3.6 – 6.2) 0.69 (0.45 – 1.05) 0.65 (0.41 – 1.01)
24m OS rate
(89/125 events)		 48.8% (30.6 – 67.0) 29.7% (19.7 – 39.7) 0.58 (0.34 – 0.99) 0.52 (0.30 – 0.90)

* Adjusted for IMDC risk group and histology (clear cell vs non-clear cell)

 

Sumanta K. Pal, David F. McDermott, Michael B. Atkins, Bernard Escudier, et al.

Patient-reported outcomes (PROs) in IMmotion150: Atezolizumab (atezo) alone or with bevacizumab (bev) versus sunitinib (sun) in first-line metastatic renal cell carcinoma (mRCC).

Conclusions: PROs suggest that atezo alone or with bev maintained daily function with minimal symptom interference vs sun. Clinical activity, safety and PRO data for atezo support its investigation in adjuvant tx of high-risk RCC pts (IMmotion010; NCT03024996). Clinical trial information: NCT01984242

TTD: HR (95% CI) vs Sun.
  Atezo Atezo + Bev
MDASI core symptom severity 0.39 (0.22, 0.71) 0.74 (0.45, 1.20)
MDASI RCC symptom severity 0.22 (0.12, 0.41) 0.60 (0.38, 0.94)
MDASI symptom interference 0.36 (0.22, 0.58) 0.70 (0.47, 1.04)
BFI fatigue severity 0.48 (0.33, 0.70) 0.75 (0.53, 1.06)
BFI fatigue interference 0.38 (0.24, 0.60) 0.67 (0.46, 0.99)

 

Igal Kushnir, Naveen S. Basappa, Sunita Ghosh, Aly-Khan A. Lalani, et al.

Conclusions: Based on the largest analysis of AS in mRCC to date, our data suggest that a subset of pts may be safely observed without immediate initiation of systemic therapy. Prospective validation is required in the contemporary immunotherapy era.
 
Hamid Emamekhoo, Mark Olsen, Bradley Curtis Carthon, Alexandra Drakaki, et al.
Conclusions: In pts with aRCC and brain metastases who are often excluded from clinical trials, NIVO + IPI treatment showed a safety profile consistent with previous reports of this dosing regimen, with encouraging antitumor activity. Clinical trial information: NCT02982954
 
Bradley Alexander McGregor, Matthew T Campbell, Wanling Xie, Arlene O. Siefker-Radtke, et al.
Conclusions: Nivolumab and ipilmumab resulted in objective responses in a subset of patients with BCVH with manageable toxicities. Updated clinical and correlative data will be presented. This combination may warrant further investigation in patients with BCVH, which has substantial unmet needs. Clinical trial information: NCT 03333616.
 
Cora N. Sternberg, Axel Stuart Merseburger, Ernest Choy, Daniel E. Castellano, et al.

Conclusions: OS and ORR appear more favorable in IC 2/3 vs IC 0/1 subgroups (overall and in the IMvigor211-like population). Atezo was effective and well tolerated across subgroups including elderly pts. Clinical trial information: NCT02928406

Endpoint All pts, PD-L1
 IMvigor211-like, PD-L1
 All pts, age
IC 0/1 (n=666) IC 2/3 (n=268) IC 0/1 (n=427) IC 2/3 (n=176) ≥65 y (n=624)a ≥75 y (n=227)a ≥80 y (n=78)a
Deaths, n (%) 388 (58) 132 (49) 235 (55) 82 (47) 335 (54) 128 (56) 44 (56)
Median OS, months (95% CI) 7.9 (6.8–9.1) 11.6 (8.8–18.8) 9.0 (7.8–10.4) 14.5 (9.5–18.8) 8.5 (7.5–10.9) 8.3 (7.3–10.9) 8.3 (5.4–11.2)
6-month OS rate, % (95% CI) 57 (53–61) 67 (61–72) 61 (56–66) 72 (65–78) 60 (56–64) 61 (54–67) 59 (47–69)
ORR, % (95% CI) 10 (8–13) 21 (16–26) 10 (7–13) 23 (17–30) 14 (12–17) 13 (9–18) 8 (3–16)

aSubgroups not mutually exclusive

E-POSTER

 

Hemant Phatak, Ruth Kim, Ting Yu, Jill Dreyfus, et al.

Real-world outcome study among patients with renal cell carcinoma (RCC) receiving checkpoint inhibitors (CPIs).

Conclusions: The majority of RCC patients receiving a CPI, mostly anti-PD-1 agents, experienced an irAE, and patients with irAEs had a higher comorbidity burden than those without irAEs. Most patients with irAEs reinitiated CPI treatment within 90 days.

 

Michal Mego, Daniela Svetlovska, Michal Chovanec, Katarina Rejlekova, et al.

Phase II study of avelumab in multiple relapsed/refractory testicular germ cell cancer.

Conclusions: This study failed to achieve its primary end point and our data suggest lack of Avelumab efficacy in unselected multiple relapsed/refractory TGCTs. Clinical trial information: NCT03403777