Escudier B, et al. Ann Oncol 2012;23(suppl. 7):vii65-vii71.
• Irrespective of the agents used in 1st line, 75-80% of advanced RCC
patients will obtain a clinicall significant benefit (i.e., a DCR):
– 84% with Sunitinib1
– 77% with Bevacizumab + IFN2
– 68% with Pazopanib (including 1st and 2nd line patients)3
• Besides those, unfortunate 20-25% who will not respond to anything,
succumbing to the disease quite soon, the vast majority of patients will
receive more than one line of treatment
• Furthermore, with few exceptions, combinations of molecularly
targeted agents proved to be too toxic
1. Motzer RJ, et al. NEJM 2007; 2. Escudier B, et al. Lancet 2007; Sternberg CN, et al. J Clin Oncol 2010
Escudier B, et al. Ann Oncol 2012;23(suppl. 7):vii65-vii71.
RECORD-11
N= 277
PFS
Everolimus
4.9
p = <0.001
N= 139
1.9
Placebo
AXIS2
N= 361
Axitinib
6.7
p = <0.0001
N= 362
Sorafenib
4.7
INTORSECT3
N= 259
Temsirolimus
4.3
p = not significant
N= 253
3.9
Sorafenib
0
5
10
(Months)
15
20
1. Motzer RJ, et al. Cancer 2010;116:4256–65; 2. Rini BI, et al. Lancet 2011;378:1931–9; 3. Hutson TE, et al. ESMO 2012;abstract LBA22
25
RECORD-11
N= 277
PFS
Everolimus
OS
14.8
4.9
OS: p = not significant
N= 139
1.9
Placebo
14.4
AXIS2,3
N= 361
Axitinib
N= 362
Sorafenib
20.1
6.7
4.7
OS: p= not
significant
19.2
INTORSECT4
N= 259
Temsirolimus
N= 253
Sorafenib
12.3
4.3
16.6
3.9
0
OS: p=0.014
statistically significant
5
10
(Months)
15
20
1. Motzer RJ, et al. Cancer 2010;116:4256–65; 2. Rini BI, et al. Lancet 2011;378:1931–9; 3. Hutson TE, et al. ESMO 2012;abstract LBA22
25
Stenner F, et al. Oncology 2012;82:333-40.
1. Motzer RJ, et al. Lancet 2008;372:449-56; 2. Motzer RJ, et al. Cancer 2010;116:4256-65.
1st Line
2nd Line
3rd Line
1st Line
2nd Line
3rd Line
1st Line
2nd Line
1st Line
mTOR
2nd Line
mTOR
3rd Line
4th Line
mTOR
4th Line
mTOR
5th Line
n = 82
n = 104
79%
n = 141
n = 89
21%
1. Motzer RJ, et al. Lancet 2008;372:449-56; 2. Motzer RJ, et al. Cancer 2010;116:4256-65;
3. Calvo E, et al. Eur J Cancer 2012;48:333-9.
Beware of time-lead bias
HR = 0.32 in both cases
Calvo E, et al. Eur J Cancer 2012;48:333-9.
Probably, Sorafenib and Sunitinib
are both effective in this setting3,4
TKI/VEGF
inhibitor
mTOR
inhibitor
Level of evidence: 1,
Grade of recommendation: A1
TKI/VEGF
inhibitor
Level of evidence: 2,
Grade of recommendation: B
TKI/VEGF
inhibitor
Level of evidence: 1,
Grade of recommendation: A2
?
mTOR
inhibitor
Level of evidence: 1,
Grade of recommendation: A1
We do now know that Everolimus is as effective
after 1 TKI, as it is after both1
1. Motzer RJ, et al. Lancet 2008;372:449-56; 2. Rini BI, et al. Lancet 2011;378:1931-9; 3. Di Lorenzo G, et al. Eur Urol 2010;58:906-11;
4. Porta C, et al. Abs. ECCO/ESMO 2011 (abs. 7131) and manuscript submitted.
Looked
smartsmart
…
… no
longer
Porta C, et al. EJMCO 2010;2:1-6.
• From large retrospective series1-3 we now know that:
– … in TKI-primary refractory patients (irrespective of the definition used),
shifting to a drug with a different mechanism of action (i.e., a mTOR
inhibitor) is not only unuseful, but also potentially detrimental1-3
– … continuing the same TKI on which tumor has progressed could be even
better than shifting to a different drug3
• From another large retrospective European cooperative series4, we
now know that:
– … in those patients who have had a clear-cut and long-lasting benefit from
a first-line TKI, no significant PFS differences were observed in second-line,
irrespective of the agent used (either another TKI, or a mTOR inhibitor)1
1. Vickers MM, et al. Urology 2010;76:430-4; 2. Heng DY, et al. Ann Oncol 2012;23:1549-55;
3. Albiges L, et al. (manuscript submitted); 4. Elaidi RT, et al. (manuscript submitted).
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