survival is eight months. I want those patients to start on
the drug tomorrow.
Q: Let’s touch upon second-line therapy. What guidelines
can you offer there?
Dr Vogelzang: In the second line we’re looking at a lot of
cabozantinib use. It’s the go-to drug for a patient who
progresses through nivo-ipi. In the last four months I
have had three patients with no response to nivo-ipi. One
of the patients is already dead—died in less than four
months. We’re not curing these poor-risk patients. If the
patient rapidly progresses on nivo-ipi, I’ll give them
cabozantinib. And even cabozantinib, although a great
drug, will have an uphill battle to delay cancer progression.
Here’s another case: one of my poor-risk patients
is an architect but his disease progressed rapidly through
nivo-ipi. When I put him on cabozantinib, he had a 3 cm
neck node. It has decreased to about 1.5 cm. It’s still there
and feel it every time I see him. He has a big primary
intact, lots of nodal disease and lung metastases. If
cabozantinib fails, I will use lenvatinib/everolimus next.
My current sequence tends to be nivo-ipi, second line
cabozantinib, and third line lenvatinib/everolimus.
Q: Among the abstracts attracting interest was the TIVO-
3 study involving tivozanib. Do you find this intriguing
despite the troubled history of the drug in seeking FDA
approval?
Dr Vogelzang: It’s a wonderful drug. The latest results are
positive but unfortunately the FDA has withheld approval
because of the initial trial where there was inequality in
survival due to differential use of second line therapy. It
is ironic that it has been approved in Europe. Tivozanib
is like other high-potency anti-VEGF agents, lenvatinib
and axitinib and would be expected to combine well with
immune check point inhibitors.
Q: You have shared your excitement about the new
combinations and as we look toward future directions,
what is the most pressing need to be addressed by studies
before the next GU ASCO meeting?
Dr Vogelzang: It’s an exciting time with improvements in
PFS and OS but we still are not able the cure the vast
majority of patients with metastatic RCC. The next steps
are to compare these various regimens (likely in the cooperative
groups), focus on the poor risk patients where progress
can be quickly measured and work on 3 drug regi-
mens such as nivo/ipi/cabozantinib or nivo/ipi/axitinib.
Selected Key Abstracts from the
GU ASCO Kidney Cancer Meeting
Editor’s note: abstracts presented here are in abbreviated
form. For the full abstracts, please visit the following link:
https://meetinglibrary.asco.org/session/11665
Thirty-month follow-up of the phase III
CheckMate 214 trial of first-line nivolumab +
20 Kidney Cancer Journal
ipilimumab (N+I) or sunitinib (S) in patients (pts)
with advanced renal cell carcinoma (aRCC).
Nizar M. Tannir, Osvaldo Arén Frontera, Hans J.
Hammers et al.
Background: N+I showed superior OS v S in ITT (IMDC
any risk) and intermediate/poor-risk (I/P) pts with aRCC
in CheckMate 214 at 17.5 mo min follow-up.
Methods: Pts with clear cell aRCC were randomized 1:1
to N3 mg/kg + I1 mg/kg Q3W×4 and then N3 mg/kg
Q2W, or S 50 mg daily for 4 wk on, 2 wk off. Co-primary
endpoints were OS, RECISTv1.1 ORR and PFS per IRRC in
I/P pts. PFS and ORR were assessed by investigator (inv)
at 30 mo.
Results: At 30 mo min follow-up, OS remains significantly
improved in ITT and I/P pts with N+I v S; the HR
for OS in favorable (fav) risk pts has improved for N+I v
the previous analysis (1.22 95% CI 0.73–2.04 v 1.45
99.8% CI 0.514.12). Per previous IRRC ORR (N+I, 42%
95% CI 3747; S, 27% 95% CI 2231), ORR per inv was
higher with N+I v S in ITT and I/P pts. ORR CIs
overlapped in fav pts, CR was doubled with N+I v S.
Increasing PFS benefit with N+I v S is emerging in ITT and
I/P pts; PFS CIs between arms remain overlapping in fav
pts. 15% v 9% of N+I and S ITT pts remain on therapy,
and 48% v 61% have received 2nd-line systemic therapy;
39% of S pts received subsequent immune-checkpoint
inhibitor therapy. Among pts who were alive with CR,
50% v 10% remain on treatment with N+I (n = 56) v S (n
= 10). 5 N+I and 7 S additional pts developed Gr 3–4 drugrelated
AEs; 1 N+I and 3 S additional pts had AEs leading
to discontinuation. No new drug-related deaths occurred.
Conclusions: At 30 mo min follow-up, OS and ORR
remain improved with N+I v S in ITT and I/P CheckMate
214 pts. No new safety signals emerged with longer
follow-up. Clinical trial information: NCT02231749
Results of a phase II study of atezolizumab and
bevacizumab in non-clear cell renal cell carcinoma
(nccRCC) and clear cell renal cell carcinoma with
sarcomatoid differentiation (sccRCC).
Rana R. McKay, Bradley Alexander McGregor, Kathryn
Gray, et al
Background: The combination of atezolizumab and
bevacizumab has demonstrated safety and efficacy in
ccRCC. In this multicenter, phase II, open-label, single
arm trial we evaluate the efficacy of atezolizumab and
bevacizumab in patients with nccRCC and sccRCC with
>20% sarcomatoid differentiation.
Methods: Eligible patients had an ECOG performance
status of 0-2 and may have received prior therapy. Prior
PD-1/PD-L1 therapy was not allowed. Patients underwent
a mandatory baseline biopsy and subsequently received
atezolizumab 120 mg and bevacizumab 15 mg/kg intravenously
every 3 weeks. Patients remained on therapy
until radiographic progression, unacceptable adverse
events, or withdrawal. The primary end point was overall
response rate (ORR) as determined by RECIST version 1.1.
Results: 65 patients were enrolled of whom 52 had ≥1
response assessment and were included in this analysis.
36 patients had nccRCC (papillary n=14, chromophobe
n=8, unclassified RCC n=3, collecting duct n=3, trans
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