complete remission is a reachable goal in mrcc - kca … · 2014-05-14 · complete remission is a...

Eighth European International

Kidney Cancer Symposium Budapest – 03-04 May 2013

Complete Remission is a Reachable Goal in mRCC

L. Albiges

Institut Gustave Roussy



Is complete remission an achievable goal in mRCC?

• Lessons from observation

• Lessons from immunotherapy

• Current status in VEGFR/mTOR targeting therapy

• Coming steps



73 year old lady

11/2000: Kidney tumor with pleural effusion and lung nodules

Pleural biopsy showed pleural mets

Nephrectomy performed: clear cell RCC, grade 2

Lessons from clinical case



11/2000

2/2001

Control CT scan performed before systemic

treatment



11/2000

2/2001

2/2009






• Current status in VEGFR/mTOR targeting therapy

• Coming steps



Immunotherapy ERA

Yes CR is achievable and immune response is involved

Study Treatment n Complete Remission

(%)

Median CR

duration

(months)

MRC

Lancet 1999

IFN vs MPA 335 2%

Pyrhonen

JCO 1999

IFN-vbl vs Vbl 160 8%

(7/80)

6

(3-65)

Motzer

JCO 2000

IFN-cRA vs IFN 284 5% (5/139)

1% (1/145)

4%

Fisher

Can J Sci Am 2000

IL2HD 255 7%

(17/255)

80

(7-131)

Atzpodien

Cancer 2002

IL2- & IFN (+5FU or 13cRA) 443 8%

(37/443)

13 years

Coppin

CochraneDatabase 2005

Meta analysis of randomized

study with IFN

6117 4%

51 study/53

Négrier

Cancer J Sci Am. 2000

4 studies <8% Up to 5 years

Figlin

Cancer J Sci Am. 1997

6%

(12/203)

36



Immunotherapy ERA

Yes CR is achievable and immune response is involved

• Identification of predictive factors for CR? – Factors of prolonged CR (predictive of CR duration)

• Number of metastatic site

• Cytoreductive Nephrectomy

• IL2 HD vs non HD

– Biological factors

• SELECT trial McDermott, ASCO JCO210

Elias, Oncology 2001






• Current status in VEGFR targeting therapy

• Coming soon



• Achievable with medical treatment only?

– incidence among phase III? • <1% across all

– Mecanism of action? • VEGFR target, tumor cell effect

• Immuno-modulation

– Neo adjuvant data? No pCR!

VEGFR TKI era



VEGFR TKI era

n Description References

Retrospective cohort Case report

3 (3/74=4%)

2

2 TKI alone 1 TKI + surgery TKI sustained subsequently( RC>22mois) Potential predictive factor: Good Pstic & intermediate, lung mets, first line, early response 2 TKI + surgery

Heng DY, Clin Genitourin Cancer. 2007 Rini B Clin Genitourin Cancer. 2006

Case report 1 TKI+ surgery ( unifocal lung met) + TKI subsequent 1y Relapse at 6 months, same site RC at TKI rechallenge and substequently sustained

Calvo OF , Anticancer drugs, Jan 2010

Case report 1 1 met site only TKI alone Treatment discontinued for toxicity

García-Campelo R , Anticancer drugs, Jan 2010

What predictive factors of CR?

Should pt stay under treatment after CR?

What kind of CR? medical/ multimodal



n Caractéristiques Références

Retrospective study 12 (12/266= 4%)

6 TKI alone 6 TKI + surgery Median FU 8.5 m; TTP: 6 mo 5/12 relapse (41%) 100% PR or SD at TKI re-introduction

Johanssen M, Eu Urol , Jun 2009

Retrospective study 5 (5/194=2.5%)

5 ccRCC 2 TKI alone 3 TKI + surgery 4/5 case : TKI discontinuation, 1/5 TKI continuation Median FU 24 mo, no relapse

Staehler M , Urol Oncol , Mar 2010

Retrospective study 36 (*12 + 24)

16 TKI alone 20 TKI+ local treatment 34/36 ccRCC Favorable pstic 39%, intermediate pstic: 61% 22 sunitinib; 11 sorafenib; 2 bevacizumab; 1 temsirolimus Median time to CR: 12mo Relapse: 24/36 ( 66,7%) TKI efficacy at re-introduction: PR or SD: 87% 12 Pt without relapse with 12mo median FU Median of drug – off period: 7m

Johannsen M, Ann Oncol 2011



• Multicenter • Retrospective analysis • Patient developping CR

– With VEGFR-TKI alone – With VEGFR-TKI plus local treatment

• Double radiological review

Aim at:

- Description CR incidence, profil

- Description of management

- Identify predictive marquers



J Clin Onco 2012

CR with systemic therapy

TKI discontinuation (n=16 ; 44%)

CR with VEGFR TKI alone (n=36)

TKI continuation (n=8 ; 22%)

TKI discontinuation

after additional cycles (n=12; 33%)

Median duration of TKI after CR obtention= 3.9 months (range 1.06–32.5)

Relapse (n=7/16 ; 44%)

Relapse (n=4/12 ; 33%)

Relapse (n=1/8 ; 13%)



TKI discontinuation (n=16 ; 44%)

CR with VEGFR TKI alone (n=36)

TKI continuation (n=8 ; 22%)

TKI discontinuation after

additional cycles (n=12; 33%)

Media duration of TKI after CR obtention = 3.9 months (range 1.06–32.5)

Relapse (n=7/16 ; 44%)

Relapse (n=4/12 ; 33%)

Relapse (n=1/8 ; 13%)

J Clin Onco 2012

CR with systemic therapy Median time to CR: 12.6 mo

range [2-28]

12/36 relapsed (33%)

Median time from CR to relapse:

7.9 months [3-32]

17/28 pts (61%) with treatment

discontinuation had prolonged

with median FUp 8.5mo



BL

08/01/08



BL

08/01/08

06/06/08



BL

08/01/08

06/06/08

05/01/09

BL

08/01/08



CR with VEGFR TKI + local ttt

(n=28)

TKI discontinuation (n=19)

TKI continuation (n=3)

TKI discontinuation after additional cycles

(n=6) Median duration of TKI administration

after CR obtention = 3.5 months

(range 1.0–15.4)

Relapse (n=10/19 ; 52%)

Relapse (n=3/6 ; 50%)

Relapse (n=1/3 ; 33%)

J Clin Onco 2012

CR with multimodal approach




(n=28)




(n=6) Median duration of TKI

administration after CR obtention = 3.5 months

(range 1.0–15.4)

Relapse (n=10/19 ; 52%)

Relapse (n=3/6 ; 50%)

Relapse (n=1/3 ; 33%)

J Clin Onco 2012

CR with multimodal approach

Site of local treatment n=28 %

Lung LN Adrenal Pancreas Gastric/Colon Other (liver…)

13 4 5 2 2 3

46 14 18 7 7

11

Among the 22 surgical samples:

NO pathological CR was observed




(n=28)




(n=6) Median duration of TKI

administration after CR obtention = 3.5 months

(range 1.0–15.4)

Relapse (n=10/19 ; 52%)

Relapse (n=3/6 ; 50%)

Relapse (n=1/3 ; 33%)

J Clin Onco 2012

CR with multimodal approach Median time to CR: 18.5 mo

range [5-45]

14/28 relapsed (50%)

Median time from CR to relapse:

8.2 months [3-25]

12/25 pts (48%) with treatment

discontinuation had prolonged

with median FUp 10.7mo



• CR: Population

– Can be obtained in all prognosis group

– Can be obtained in various and multiple metastatic profil

– No predictive identified factors

• CR: feasibility of drug interruption

– Cons: – Any proof of delaying recurrence?

– Potential rebound?

– Pros: – Quality of life,

– prevention of drug resistance

– cost

– Efficacy of drug re-introduction at relapse

CR with TKI : Conclusion (1/2)

18 patient received subsequent VEGFR i

(14 same TKI, 4 alternative TKI):

• 10 PR

• 4 SD

• 1 PD

• 3UKN

J Clin Onco 2012



CR: Proposed management

• TKI alone CR: sustained 3 months of TKIs after CR then drug arrest

• Multimodal CR: no « adjuvant » TKI after local treatment

• Follow up:

– CT- scan every 3 months during first year

– and then every 6 months

CR with TKI : Conclusion (2/2)

J Clin Onco 2012



CR with TKI : Next step

ANALYSE PROSPECTIVE DES REMISSIONS COMPLETES OBSERVEES

SOUS SUNITINIB CHEZ DES PATIENTS ATTEINTS D’UN CANCER DU

REIN METASTATIQUE (mRCC)

• Prospective national study – Case - control design study

– multicentric

– Central Radiological review

– Tissue collection

– Blood sampling at time of CR and relapse

N = 120: 40 case, 80 control pts



CR : Coming soon… • Not obtained with combination of current VEFR/mTOR agents

• What about new agents alone or new combinations?

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« It is ethical to believe in it!»

Dr Besse

complete remission is a reachable goal in mrcc - kca … · 2014-05-14 · complete remission is a...

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