Highlights from ASCO 2019
Incremental But Significant Progress Offers
Glimpse of New Directions as IO Combinations
Still Dominate the Treatment Narrative
Kidney Cancer Journal 53
s new data continued to emerge, and new combinations
of drugs gained regulatory approval for renal cell
carcinoma (RCC), the world of cancer, represented by
an estimated 40,000 attendees, convened in Chicago for the
55th annual meeting of the American Society of Clinical Oncology
(ASCO). Although no major blockbuster revelations in
RCC emerged, several updates from important large trials were
presented, and interesting data from several smaller studies
were discussed.
Immunotherapy Combinations Effective
in Variant Histologies
Echoing the trend toward immunotherapy combinations,
several studies presented subset analysis and updated results
from various studies of immunotherapy and immunotherapy
combinations. Among these was a subgroup
analysis of patients with untreated metastatic RCC and
sarcomatoid histology from the IMmotion151 study. The
study analyzed 142 patients (16% of total enrolled subjects)
who had any component of sarcomatoid histology.
This analysis found a longer overall survival, improved
progression- free survival (8.3 vs 5.3 months), and a higher
overall response rate (49% vs 14%) in sarcomatoid patients
treated with atezolizumab + bevicizumab vs
sunitinib, regardless of PD-L1 status.
Similarly, Flippot et al reported the results of a phase
II study which tested atezolizumab + bevicizumab in 60
patients with non-clear cell RCC and clear cell RCC with
sarcomatoid differentiation. Among 56 patients evaluable
for response, overall response rate was 53% in the
sarcomatoid patients and 26% in those with non-clear
cell RCC. Median progression-free survival was 8.4
months in the overall population, suggesting efficacy of
this combination in patients with these variant histologies.
CheckMate 214: Implications for Risk Stratification
Bernard Escudier and colleagues performed post hoc analysis
of CheckMate 214, comparing efficacy of nivolumab
combined with ipilimumab vs sunitinib by number of
IMDC risk factors present. They found the efficacy of immunotherapy
was consistent regardless of the number of
risk factors present, while the efficacy of sunitinib worsened
in patients with more risk factors, suggesting that traditional
risk models for RCC are likely less accurate in the
immunotherapy era.
KEYNOTE-427 and KEYNOTE 426
Although most studies focused on immunotherapy combinations,
Tykodi and colleagues presented updated results
from the clear cell RCC cohort of KEYNOTE-427, an
open-label, single-arm, phase 2 study of first-line singleagent
pembrolizumab. Of 110 patients enrolled, overall
response rate was 36.4% in all patients and 44.2% in patients
who were positive for PD-L1 with 3 patients (2.7%)
achieving a complete response. Median progression-free
survival was 7.1 months (95% CI, 5.6-11.0) and median
overall survival was not reached. Toxicities were as expected.
The non-clear cell cohort of KEYNOTE-427 was
presented as a separate poster. 165 patients with nonclear
cell RCC received pembrolizumab and were found
to have an overall response rate of 24.8%. 12 month progression
free survival was 22.8% and the 12 month overall
survival rate was 72.0%, echoing other emerging data
which suggests the efficacy of the immunotherapy in patients
with non-clear cell RCC and RCC with sarcomatoid
differentiation.
Similarly, a subgroup analysis of KEYNOTE-426 presented
by Rini et al, also showed benefit of combination
immunotherapy and targeted therapy in a combined population
of patients with IMDC intermediate or poor risk
RCC and patients whose tumors had sarcomatoid features.
68.8% of all randomized patients in the study had
IMDC intermediate or poor risk disease (294 in the pembrolizumab
plus axitinib arm and 298 in the sunitinib
control arm). The combination of pembrolizumab plus
axitinib improved overall survival (12-mo rate 87.3% vs
71.3%), median progression free survival (12.6 vs 8.2
Marc R. Matrana, MD, MS, FACP
Precision Cancer Therapies Program
Ochsner Cancer Institute
New Orleans, Louisiana
A