Papillary News from ASCO 2010

[Rose Woodward]

jay Bitkower a KC patient and Chair of "Action to Cure Kidney Cancer" has posted the following on the Kidney Onc listserv and kindly allowed me to copy it on here for our members.....

Przemyslaw Twardowski from the City of Hope Medical Center, gave an oral
presentation on the Management of Non-clear Cell Histology, which mostly
focused on papillary. There are two types of papillary histology, Type I,
for which in the sporadic (not inherited) cases there is an over-expression
of the c-Met pathway, and Type II, which is more aggressive and has no c-Met
amplification. For Type I, fewer than 10% of the cases have a c-Met mutation
but in up to 50% of the cases c-Met is over-expressed. Pre-clinical evidence
has also shown that inhibition of the EGF (epidermal growth factor) pathway
may also have an effect in pRCC.

Twardowski reviewed trial data, mostly retrospective, for pRCC, two of which
I already summarized (Plimack and Choueiri). The others were a sunitinib
(Sutent) expanded access trial for 276 non-clear cell patients by Gore
showing a progression-free survival (PFS) of 6.7 months after cytokine
(IL-2, Interferon-alpha) therapy and the subset analysis of the temsirolimus
(Torisel) Phase III trial for 55 pRCC patients, mostly with poor prognosis,
with no prior therapy, who demonstrated a PFS = 7 months. Temsirolimus is an
mTOR inhibitor and Novartis is running a trial on its m-TOR inhibitor,
everolimus (Afinitor) for pRCC patients.

Finally, Twardowski reported on a 52-patient Phase II trial of erlotinib
(Tarceva), an EGFR inhibitor, for pRCC, which showed a response rate of only
11% but a median overall survival of 26.9 months, indicating that there was
enough response to indicate further study.

Then Twardowski turned to the most promising area, the c-Met pathway for
Type I pRCC. The Phase II trial of GlaxoSmithKline's compound foretinib for
which preliminary results were reported last year, was notable in that 80%
of the patients showed some tumor shrinkage (from 4-35%). Final trial
results for this trial may be out late this year.

Twardowski noted other agents exhibiting c-Met inhibition, some of which are
in trials for solid tumors and lung cancer. They are: ARQ-197, K-252A,
SU11274, PHA-665752, SGX523, and MP470. A couple of monoclonal antibodies
are AV299 and AMG 102. He also listed current studies using targeted agents
for pRCC patients: a 92-patient first line trial of sunitinib in France, a
41-patient first line trial using bevacizumab (Avastin) in the US, the
60-patient first line trial using everolimus in Europe, a 40-patient first
to third line trial of the combination of bevacizumab and erlotinib in the
US (also testing HLRCC (hereditary papillary cancer) as well as sporadic
pRCC patients); and for non-clear cell patients, a 108 patient first-line
trial testing sunitinib versus everolimus in the US, and finally a
27-patient first or second-line trial testing bortezomib (aka Velcade and
is approved for multiple myeloma treatment) in the US. NB: the 108-patient
trial is not open yet, and the 27-patient trial seems to have closed a year
ago with no results published.

Twardowski summarized his presentation by concluding that, aside from the
c-Met and EGFR inhibitors, there is some evidence that temsirolimus benefits
patients with non-clear cell histology, the tyrosine kinase inhibitors
(sunitinib, sorafenib) have activity, but there is no evidence that
bevacizumab, Interleukin-2, or Interferon-alpha have any effect.

Jay Bitkower

Action to Cure Kidney Cancer

www.ackc.org