Brielle Benyon

Real-world data presented during the 2021 ESMO Congress showed longer survival outcomes among patients with renal cell carcinoma (RCC) and prior VEGF-targeted therapy who received single-agent cabozantinib (Cabometyx) versus single-agent axitinib (Inlyta) in the second-line setting or later.

The retrospective cohort study analyzed outcomes from Public Health England’s Cancer Analysis System of adults who were diagnosed with stage III or IV RCC between January 1, 2011, and December 31, 2018, with follow-up lasting until January 31, 2020. A total of 440 patients received cabozantinib treatment, while 1045 received axitinib.

Median duration of treatment was longer for those who received cabozantinib (5.52 months; IQR, 2.73-11.74) than those on axitinib (4.60 months; IQR, 1.45-12.36).

Patients on the TKI inhibitor cabozantinib also had numerically longer median overall survival (OS) than patients given axitinib. In the unweighted analysis, median OS for cabozantinib was 11.41 months (IQR, 5.65-27.32) compared with 9.60 months (4.54-20.32). Similar results were found in the IPW analysis, with average OS lengths of 11.24 months (IQR, 5.65-27.98) and 10.39 months (IQR, 4.70-20.03) for the cabozantinib and axitinib arms, respectively.

“Both agents have been approved in the U.K. as second or later line treatment options for patients with advanced RCC—axitinib since 2012, and cabozantinib since 2016,” said study author Janet Brown, MB BS, MSc, MD, FRCP, Professor of Translational Medical Oncology at University of Sheffield, in her presentation of the data.

Notably, patients in the cabozantinib arm tended to have a more recent diagnosis, with 65% receiving a diagnosis between 2016 and 2018. Conversely, 80% of those on axitinib were diagnosed before 2016. In the United States, cabozantinib was approved by the FDA in December 2017 for first-line treatment, based on findings from the CABOSUN (NCT01835158) trial, which showed improved progression-free survival over sunitinib (Sutent), at 8.6 months and 5.3 months, respectively.

Characteristics between the cabozantinib and axitinib patient groups were otherwise balanced, with the average age being 62.5 years and 63.0 years, respectively. At diagnosis, 58.6% of patients in the cabozantinib cohort and 53.2% of those on the axitinib cohort had metastases, while 91.4% and 90.3%, respectively, had clear-cell histology. Regarding tumor size at diagnosis, 69.3% and 68.8% were 4.00 mm or smaller, in the cabozantinib and axitinib arms, respectively; 5.9% and 7.1% had tumors larger than 4.00 mm, and the remainder (24.8% and 24.1%) of patients had missing tumor sizes.

At diagnosis, 28.2% of patients given cabozantinib had an ECOG score of 0-1, compared with 20.4% of those on axitinib.

“Real-world evidence complements the results of randomized controlled trials,” Brown said. “This study demonstrates the potential for cabozantinib for conducting clinically relevant real-world research in England.”

1. Brown J, Harrow B, Marciniak A, McCarthy C, Cirneanu L, Protheroe A. Cabozantinib and axitinib after vascular endothelial growth factor therapy in patients with advanced renal cell carcinoma: a retrospective cohort study. Presented at: ESMO Congress 2021. September 16-21, 2021. Virtual. E-Poster 680P.

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The retrospective cohort study assessed outcomes in patients with advanced renal cell carcinoma who received cabozantinib or axitinib in the second-line setting or beyond. 

Real-world results suggest survival advantage with cabozantinib versus axitinib in pretreated kidney cancer

The novel PI3K-y inhibitor eganelisib (IPI 549) boosted response rates in patients with metastatic urothelial carcinoma (mUC) treated with nivolumab (Opdivo), according to recent research presented at the 2021 Genitourinary Cancers Symposium.

“PD-1 inhibitors have demonstrated clinical benefit in metastatic urothelial carcinoma. However, clinical benefit remains low, particularly in PD-L1–low patients, who have [an average] overall response rate of only 16%,” said study author Piotr Tomczak, MD, PhD, of the Poznan University of Medical Sciences in Poznan, Poland.

The phase II MARIO-275 study (NCT03980041) included 49 patients with mUC who progressed on 1 or more platinum-based chemotherapy regimens and had no prior treatment with a checkpoint inhibitor. Study participants were stratified by baseline circulating monocytic myeloid suppressor cell (mMDSC) levels and randomized 2:1 to receive eganelisib plus nivolumab or placebo plus nivolumab.

Objective response rate (ORR) per RECIST v1.1 in patients with high baseline mMDSC levels (≥22.3) was the primary end point, and researchers also examined overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Duration of exposure was a median of 15 weeks for patients treated with – and 11 weeks for the placebo arm.

While no mMDSC-high patients responded to treatment with eganelisib, there was a higher response rate in the overall population treated with the combination regimen, compared to placebo ([30.3%; 95% CI, 16-9] vs [25%; 95% CI, 7-52], respectively). Additionally, there was a 38.5% ORR in mMDSC-low patients who received eganelisib (95% CI, 20-59), compared to 23.1% in the mMDSC-low patients who received placebo (95% CI, 5-54).

There were 5 PD-L1–positive patients (TPS >1%) in the combination treatment group, of which 4 (80%) responded to the addition of eganelisib to nivolumab (95% CI, 28-100), compared to 2 of 4 (50%) in the placebo group (95% CI, 7-93). In PD-L1–negative patients (TPS <1%) 6 out of 23 patients (26.1%) responded to the combination regimen (95% CI, 10-48), versus 1 of 7 (14.3%) in the placebo group (95% CI, 0-58). 

“The combination demonstrated improved ORR, disease control rates, and PFS when compared to the control, especially in the PD-L1–negative patients, who represent approximately 70% of the patient population,” Tomczak said.

When it came to PFS, 9.1% of patients responded on the combination therapy, compared to 8% on the placebo arm.

Common all-grade adverse events (AEs) in the eganelisib and placebo arms were pyrexia (33% vs 0%, respectively), decreased appetite (30% vs 19%), pruitis (24% vs 6%), asthenia (21% vs 31%), and transaminase elevation (21% vs 6%). The most common grade 3 or higher AEs were hepatotoxicity (15% vs 0%, respectively), transaminase elevation (12% vs 6%), and rash (9% vs 0%). After a safety review, the eganelisib dose was reduced from 40 mg to 30 mg, which lowered the rate of hepatic AEs.

“Importantly, nivolumab monotherapy in the control arm of MARIO-275 demonstrated clinical activity consistent with monotherapy with nivolumab in CheckMate-275, further adding to our confidence in interpreting the contribution of eganelisib [with] nivolumab in the controlled study,” Tomczak said.

Based on these findings, a larger study is being planned in the future to further evaluate eganelisib in PD-L1–low patients.

“Given the magnitude of unmet need in the PD-L1–low patient [population], Infinity is planning a registration and labeling study exploring the potential benefit of eganelisib for PD-L1–low patients, more broadly in other indications,” Tomczak said.

1. Tomczak T, Popovic L, Barthelemy P, et al. Preliminary analysis of a phase II, multicenter, randomized, active-control study to evaluate the efficacy and safety of eganelisib (IPI 549) in combination with nivolumab compared to nivolumab monotherapy in patients with advanced urothelial carcinoma. Presented at: 2021 Genitourinary Cancers Symposium; February 11-13, 2021; Virtual. Abstract 436.

The novel agent eganelisib led to higher response rates with nivolumab in PD-L1–low patients with metastatic urothelial carcinoma.

Brielle Benyon

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Real-world results suggest survival advantage with cabozantinib versus axitinib in pretreated kidney cancer

Eganelisib may boost response to nivolumab in mUC