Download Characterization of Patients with Poor

Characterization of Patients with PoorRisk Metastatic Renal Cell Carcinoma
Hamieh L1*, McKay RR1*, Lin X2, Simantov R2, Choueiri TK1
*Equal contributions
1Dana-Farber Cancer Institute, Boston, USA
2Pfizer Oncology, New York, USA
Fifteenth International Kidney Cancer Symposium
November 4-5, 2016
Marriott Miami Biscayne Bay, Miami, Florida, USA
www.kidneycancersymposium.com
Disclosures
The study was supported by:
• Pfizer
• Dana-Farber/Harvard Cancer Center Kidney SPORE
• Trust Family, Michael Brigham, and Loker Pinard Funds for Kidney Cancer
Research
Fifteenth International Kidney Cancer Symposium
November 4-5, 2016
Marriott Miami Biscayne Bay, Miami, Florida, USA
www.kidneycancersymposium.com
Background
• Survival outcomes are heterogeneous across different subsets of
metastatic renal cell carcinoma (mRCC) patients.
• Risk stratification models have been designed to characterize
these differences:
1. Memorial Sloan Kettering Cancer Center (MSKCC) model
2. International Metastatic Database Consortium (IMDC) model
3. Prognostic criteria used by Hudes phase III Temsirolimus trial
• The purpose of our study is to characterize poor-risk mRCC
patients defined by the three models in a large clinical trials
database.
Fifteenth International Kidney Cancer Symposium
November 4-5, 2016
Marriott Miami Biscayne Bay, Miami, Florida, USA
www.kidneycancersymposium.com
Methods
• Retrospective analysis of 4,736 mRCC patients treated on phase II/III clinical trials
sponsored by Pfizer.
• Patients meeting criteria for poor-risk disease as defined by the three models
were selected.
• OS and PFS were estimated using the Kaplan-Meier method and were assessed
using multivariable Cox regression*:
• In the total cohort
• In patients remaining on therapy > 12 months
• ORR and AEs were evaluated.
• The concordance (c-) index for each of the models was determined to assess their
prognostic performance.
*Adjusted for baseline characteristics including age, sex, race, body mass index (BMI), histology, prior nephrectomy, prior therapy, sites of metastasis and the models’
prognostic factors.
Fifteenth International Kidney Cancer Symposium
November 4-5, 2016
Marriott Miami Biscayne Bay, Miami, Florida, USA
www.kidneycancersymposium.com
Baseline Characteristics – Total Cohort
The majority of the patients were/had:
• Caucasian
• Males
• Older than 65 years
• Good performance status
• Clear-cell histology
• Lungs as the most common metastatic
site
IMDC , N(%)
MSKCC , N(%)
Hudes , N(%)
1145 (24)
904 (19)
1901 (40)
3 (3-6)
3 (3-6)
3 (3-5)
KPS<80%
461 (40)
467 (52)
533 (28)
> 3 metastases
570 (50)
499 (55)
938 (49)
No prior Nephrectomy
233 (20)
197 (22)
527 (28)
Dx to Rx <1 yr
988 (86)
852 (94)
1667 (88)
LDH > 1.5 ULN
184 (16)
280 (31)
354 (19)
Hemoglobin <LLN
1038 ( 91)
833 ( 92)
1673 ( 88)
Neutrophils > ULN
455 (40)
223 (25)
413 (22)
Platelets > ULN
594 ( 52)
355 ( 39)
590 ( 31)
Calcium > 10mg/dl
596 (52)
536 (59)
732 (39)
Poor-risk patients
Risk factors (min-max)
IMDC = International Metastatic Database Consortium; MSKCC = Memorial Sloan Kettering Cancer
Center; KPS= Karnofsky Performance Status; Dx= Diagnosis; Rx = Treatment; LLN= Lower Limit of
Normal; ULN = Upper Limit of Normal; LDH = Lactate Dehydrogenase
Fifteenth International Kidney Cancer Symposium
November 4-5, 2016
Marriott Miami Biscayne Bay, Miami, Florida, USA
www.kidneycancersymposium.com
Outcomes – Total Cohort
1.0
n
IMDC
1145
Hudes 1901
MSKCC 904
0.9
Survival Probability
0.8
Median, mo (95% CI)
8.6 (7.9–9.5)
10.6 (9.9–11.3)
7.5 (6.9–8.2)
IMDC
MSKCC
Hudes
Median OS (95% CI)
(mos)
8.6 (7.9-9.5)
7.5 (6.9-8.2)
10.6 (9.911.3)
Median PFS (95% CI)
(mos)
3.7 (3.4-3.9)
3.5 (2.9-3.7)
4.2 (3.9-4.6)
ORR (%)
10.7
10.3
14.6
Grade ≥3 AEs (%)
81.2
81.9
76.7
C-index (95% CI)
0.826 (0.7960.855)
0.830 (0.8000.858)
0.825 (0.7950.854)
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
0
10
20
30
40
Time (months)
50
60
Overall Survival of poor-risk patients defined by the MSKCC,
IMDC and Hudes prognostic models
OS = Overall Survival; CI= Confidence Interval; mos = months; PFS = Progression
Free Survival; ORR = Overall Response Rate; AEs = Adverse Events.
Fifteenth International Kidney Cancer Symposium
November 4-5, 2016
Marriott Miami Biscayne Bay, Miami, Florida, USA
www.kidneycancersymposium.com
Patients Remaining on Therapy > 12 Months
Baseline characteristics are similar
to the total cohort
IMDC
MSKCC
Hudes
117 (10)
85 (9)
257 (14)
Median OS (95% CI)
(mos)
30.7 (28.4 –
NR)
29.8 (26.1-NR)
35.2 (30.7 NR)
Median PFS (95% CI)
(mos)
17.1 (14.7 –
20.2)
17.2 (14.8 20.2)
18.3 (16.4 20.7)
42
45
53
1.0
0.9
N (%)
Survival Probability
0.8
0.7
0.6
0.5
0.4
0.3
0.2
IMDC
Hudes
MSKCC
0.1
n
117
257
85
Median, mo (95% CI)
30.7 (28.4–NR)
35.2 (30.7–NR)
29.8 (26.1–NR)
0.0
0
10
20
30
40
Time (months)
50
60
Overall Survival of poor-risk patients, defined by the MSKCC,
IMDC and Hudes prognostic models, on therapy > 12 months
ORR (%)
OS = Overall Survival; CI= Confidence Interval; mos = months; NR= Not Reached;
PFS = Progression Free Survival; ORR = Overall Response Rate.
Fifteenth International Kidney Cancer Symposium
November 4-5, 2016
Marriott Miami Biscayne Bay, Miami, Florida, USA
www.kidneycancersymposium.com
Conclusions
• The models have equivalent prognostic performance in the
era of targeted therapy.
• They should be further evaluated in the setting of newer
treatment modalities.
• Poor-risk patients continue to have dismal outcomes,
hence the dire need for alternative therapies in these
patients.
• However, a subset of poor-risk patients derived prolonged
clinical benefit.
• This subset needs to be further explored for the
identification of predictive biomarkers.
Fifteenth International Kidney Cancer Symposium
November 4-5, 2016
Marriott Miami Biscayne Bay, Miami, Florida, USA
www.kidneycancersymposium.com
Acknowledgements
•
•
•
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Kidney cancer patients and their families
Pfizer Oncology
Dana Farber Lank Center for Genitourinary Oncology
Dana-Farber/Harvard Cancer Center Kidney Cancer Program
Fifteenth International Kidney Cancer Symposium
November 4-5, 2016
Marriott Miami Biscayne Bay, Miami, Florida, USA
www.kidneycancersymposium.com