PracticeUpdate: Haematology & Oncology

Dr Pal:

You’re presenting results from the

CABOSUN clinical trial… tell us some of

the rationale for pitting sunitinib against

cabozantinib.

Dr Choueiri:

I think this is an amazing unmet

need and the National Cancer Institute and the

Alliance GU Committee, under the leadership at

that time of Eric Small and nowMichael Morris,

did recognise this important unmet need, the

intermediate and poor-risk population. …One

of the unmet needs was in front-line untreated

patients can you do more than VEGF receptor

blockade. And sunitinib as you know is the

most commonly used and highly effective drugs

front-line.

We have cabozantinib in mind because one of

the biology about cabozantinib is that the drug

not only inhibits the VEGF receptor, but does

inhibit other tyrosine kinases such as MET and

Excel, and these we know now are involved in

making mechanism of resistance and escape the

VEGF receptor inhibitor. There is significant pre-

clinical data, and at that time there was a trial

that showed cabozantinib as active in later line

of treatment.

So we launched this study. It’s a smaller study,

a randomised phase 2 but well-powered for the

primary endpoint of progression-free survival in

a population of metastatic RCC of unmet need,

which is 70 to 80% of everyone. This is the

population of intermediate and poor-risk renal

cell cancer.

Dr Pal:

I would imagine that this study is going

to have a dramatic impact on how we think

about front-line therapy. But one interesting

conundrum that I see is that many of the front-

line trials that we have designed right now pit

sunitinib against a combination of either IO and

VEGF inhibitor or two IOs together. What are

your thoughts there? Should we be looking at

combinations with cabozantinib now?

Dr Choueiri:

I think it’s very possible we should

because the field is moving very, very fast and

there is data. There is also pre-clinical data, not

just that cabozantinib works and the IO works

so the combination should work, which makes

sense, but also there’s pre-clinical data of synergy

with cabozantinib on the immune system. There

is a decrease in the Tregs which impair the

immune response and there’s an increase in CD8

T cell, so together they make more sense also

rather than just clinically, but they make more

sense biology-wise.

Dr Pal:

Another hot topic at this meeting is

adjuvant therapy for renal cell carcinoma; first

time that we’re going to see some positive data

from an adjuvant trial in the S-TRAC Study.

Not knowing the data associated with the trial,

is disease-free survival a relevant endpoint in this

setting, or should we be setting the bar higher to

overall survival? I know it’s a common concept in

oncology, what do you think?

Dr Choueiri

: This is a great question. I think when

the study was designed disease-free survival

was an acceptable endpoint that would not take

many, many years to happen based on events.

But this is a tough, tough area and I would say

it’s going to be, beside the combination and what

the front-line is going to show on new target, it’s

going to be an area the next 6 to 12 months of

intense discussion among experts because we

do have a study.

Another cooperative group study with Dr Naomi

Haas from ECOG we all participated in where

the study was completely negative, even on

subgroup analysis in high-risk patients which

is what S-TRAC is, there was no difference in

disease-free survival or overall survival. So we

need to see the data. I would be certainly more

convinced if the toxicity was acceptable and

if there are at least a trend in overall survival

because at the end of the day with surgery alone

you can cure these patients.

Remember this is not versus delayed sunitinib;

we don’t know what happens to the placebo arm.

So delaying progression, is that acceptable if

there is no overall survival and let’s say decreased

quality of life, it remains to be seen, but let’s

not forget that we, with surgery alone we can

cure patients. So we need to look at the study.

It definitely could be practice changing, but it

has to take in account the ASSURE trial, and

of course there are two studies in the adjuvant

setting that finished accrual with pazopanib and

another was sorafenib. So if these two studies

are negative let’s say, then what is going on, we

have to ask ourselves. So, look forward to seeing

the data.

Dr Sumanta Pal is an

internationally recognised

leader in the area of

genitourinary cancers.

He is the Co-Director of

the City of Hope Kidney

Cancer Program in

California and is the head

of the kidney and bladder

cancer disease team at the institution.

Dr Toni Choueiri on clinically impactful

newRCC data at ESMO 2016

Sumanta Pal MD, speaks

with Toni Choueiri MD

(above), Director of the GU

Oncology Program, Dana-

Faber Cancer Institute, on

cabozantinib and adjuvant

therapy in metastatic renal

cell carcinoma.

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EUROPEAN SOCIETY OF MEDICAL ONCOLOGY 2016 CONGRESS

PRACTICEUPDATE HAEMATOLOGY & ONCOLOGY