JOURNAL CLUB
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placebo. Higher baseline CXCL10 was associated with
worse DFS (HR 1.41 per log increase in CXCL10,
Bonferroni-adjusted P = 0.003). This remained significant
after adjustment for T-stage, Fuhrman grade, and
ECOG performance status.
Conclusion: Among patients treated with adjuvant
VEGFR TKIs for RCC, drug-host interactions mediate
changes in circulating cytokines. Elevated baseline
CXCL10 was associated with worse DFS. Studies to
understand functional consequences of these changes
are under way.
First-line Immuno-Oncology Combination
Therapies in Metastatic Renal-cell Carcinoma:
Results from the International Metastatic Renal-cell
Carcinoma Database Consortium. Dudani S, Graham
J, Wells C, et al. Eur Urol. 2019 Aug 22. pii: S0302-
2838(19)30609-8. doi: 10.1016/j.eururo.2019.07.048.
Epub ahead of print
Summary: In metastatic renal-cell carcinoma (mRCC),
recent data have shown efficacy of first-line ipilimumab
and nivolumab (ipi-nivo) as well as immuno-
oncology (IO)/vascular endothelial growth factor
(VEGF) inhibitor combinations. Comparative data
between these strategies are limited.This study compared
the efficacy of ipi-nivo versus IO-VEGF (IOVE)
combinations in mRCC, and described practice
patterns and effectiveness of second-line therapies.
Using the International Metastatic Renal-cell Carcinoma
Database Consortium (IMDC) dataset, patients
treated with any first-line IOVE combination were
compared with those treated with ipi-nivo. All patients
received first-line IO combination therapy A First- and
second-line response rates, time to treatment failure
(TTF), time to next treatment (TNT), and overall
survival (OS) were analysed. Hazard ratios were adjusted
for IMDC risk factors. In total, 113 patients received
IOVE combinations and 75 received ipi-nivo. For
IOVE combinations versus ipi-nivo, first-line response
rates were 33% versus 40% (P = 0.4), TTF was 14.3
versus 10.2 mo (P = 0.2), TNT was 19.7 versus 17.9
mo (P = 0.4), and median OS was immature but not
statistically different (P = 0.17). Adjusted hazard ratios
for TTF, TNT, and OS were 0.71 (P = 0.14), 0.65
(P = 0.11), and 1.74 (P = 0.14), respectively. Sixty-four
(34%) patients received second-line treatment. In
patients receiving subsequent VEGF-based therapy,
second-line response rates were lower in the IOVE
cohort than in the ipi-nivo cohort (15% vs 45%
(P = 0.04; n = 40), though second-line TTF was not
significantly different (3.7 vs 5.4 mo; P = 0.4; n = 55).
Limitations include the study’s retrospective design
and sample size.
Conclusion: There were no significant differences in
first-line outcomes between IOVE combinations and
ipi-nivo. Most patients received VEGF-based therapy
in the second line. In this group, second-line response
rate was greater in patients who received ipi-nivo
initially. KCJ
86 Kidney Cancer Journal