Page 5 - Management of advanced kidney cancer: KCRNC

Kcrnc consensus: advanced kidney cancer

ments can be associated with side effects and that some 2.1.1.3.2 Other options
patients may experience an indolent clinical course with The recommendation for sunitinib or pazopanib as possible,
stable or slow-growing, low-volume, and/or asymptomatic non-preferred options in the upfront setting for intermedi-
metastases. This is supported by prospective observational ate- or poor-risk come from the same data sets as described
data presented by Rini and colleagues. 60 above in the favorable-risk setting; intermediate- and poor-
risk patients were treated with VEGF-targeted TKI therapy in
2.1.1.3. IMDC intermediate- or poor-risk pivotal trials as well. The consensus was that these agents
would still be preferentially used in patients with contrain-
2.1.1.3.1 Preferred therapies dications for immunotherapy, in patients with poor clinical
condition due to extensive RCC, and in those who needed a
2.1.1.3.1.1 Ipilimumab + nivolumab more rapid response to therapy. It should also be noted that
The CheckMate 214 study was a randomized, open-label, in sunitinib-intolerant, poor-risk patients, pazopanib remains
phase 3 trial of nivolumab + ipilimumab followed by niv- an option for treatment.
9
olumab monotherapy vs. sunitinib monotherapy. The
1096 subjects enrolled in the trial were ≥18 years of age 2.1.1.3.2.1 Avelumab + axitinib
with previously untreated advanced RCC with a clear-cell JAVELIN Renal 101 was a phase 3, randomized, open-label
component. They were randomized to either nivolumab + study comparing avelumab + axitinib with sunitinib among
ipilimumab (n=550) or sunitinib (n=546). As per inclusion 886 patients with clear-cell advanced RCC and no prior
62
criteria, the majority of enrolled patients had IMDC inter- systemic therapy. All prognostic risk groups were included.
mediate- (n=425) or poor-risk (n=422). The co-primary end- The co-primary endpoints were PFS and OS among patients
points were OS, ORR, and PFS in intermediate- and poor-risk with PD-L1-positive tumors (n=560). In this group, medi-
patients. The same endpoints were used for the exploratory an PFS was 13.8 months with avelumab plus axitinib vs.
cohort of favorable-risk patients. 7.2 months with sunitinib (HR 0.61; 95% CI 0.47–0.79;
After a median followup of 25.2 months, among inter- p<0.001). In the overall population, the median PFS was
mediate-/poor-risk patients, the ipilimumab-nivolumab arm 13.8 months vs. 8.4 months (HR 0.69; 95% CI 0.56–0.84;
was associated with improvements in all three co-primary p<0.001). OS data for this study were immature at the data
endpoints. ORR was 42% vs. 27% (p<0.001), including cutoff, with a suggestion of benefit for avelumab + axitinib,
complete responses in 9% vs. 1% for ipilimumab + niv - but no statistical significance to date (HR 0.78; 95% CI
olumab vs. sunitinib, respectively. Median PFS at the time 0.55–1.08; p=0.0679).
of the primary data report was 11.6 for ipilimumab + niv- Axitinib is currently only approved in Canada as mono-
olumab and 8.4 months for sunitinib (HR 0.82; p=0.03, not therapy after failure of prior systemic therapy with either a
statistically significant), and median OS was not reached for cytokine or sunitinib. Avelumab is not currently approved
ipilimumab + nivolumab and 26 months for sunitinib (HR in Canada for mRCC (although it has indications for other
0.63; p<0.001). A data update presented at GU-ASCO 2019 malignancies).
and recently published showed that these trends continued
out to 30 months’ followup. Numerically, the proportions 2.1.1.3.2.2 Bevacizumab + atezolizumab
61
of patients achieving a complete response (CR) seems to be IMmotion151 was a phase 3, randomized, open-label study
increasing and has reached 11% with the longer followup. comparing bevacizumab + atezolizumab with sunitinib in
Among favorable-risk patients, there has not been any sig- 915 patients with mRCC and a component of clear-cell or
nificant difference demonstrated between the treatment arms sarcomatoid RCC. The median OS in the intention-to-treat
63
for PFS or OS. population was 33.6 months vs. 34.9 months (HR 0.93;
p=0.4751), indicating there is no statistically significant ben-
2.1.1.3.1.2 Pembrolizumab + axitinib efit over suntinib. The median PFS in the intention-to-treat
The clinical trial informing this recommendation is population was 11.2 vs 8.4 months (HR 0.83; p=0.02190).
10
KEYNOTE-426, described above. The primary endpoint of At interim analysis, the median OS in the PD-L1-positive
the study was in the unselected overall population, including population was 34.0 months vs. 32.7 months (HR 0.84;
patients with intermediate-/poor-risk (n=592) and with favor- p=0.2857) and in the PD-L1-positive population, the medi-
10
able-risk (n=269). The overall data are reported above. an PFS was 11.2 months in the atezolizumab/bevacizum-
With respect to IMDC risk groups, subgroup analysis showed ab group vs. 7.7 months in the sunitinib group (HR 0.74;
that pembrolizumab + axitinib was associated with an OS p=0.0217). Neither drug is approved in Canada for the treat-
improvement in intermediate- (HR 0.53; 95% CI 0.35–0.82) ment of mRCC.
and poor-risk (HR 0.43; 95% CI 0.23–0.81) groups.

CUAJ • October 2019 • Volume 13, Issue 10 347