IMmotion151 research final OS results released

Introduction With the rapid development of immunotherapy, combined immune targeted therapy has become one of the main first-line treatment options for metastatic renal cell carcinoma
.

The interim analysis of the IMmotion151 study showed that atilizumab + bevacizumab compared with sunitinib can significantly improve the progression-free survival (PFS) of patients, reaching the primary study endpoint
.

Recently, the study announced the final overall survival (OS) results and the results of exploratory analysis of biomarkers
.

Background The IMmotion151 study is a multi-center, open-label phase III clinical study, which aims to evaluate the efficacy and safety of atilizumab + bevacizumab versus sunitinib for the initial treatment of metastatic renal cell carcinoma
.

The interim analysis showed that compared with sunitinib, atilizumab + bevacizumab can significantly prolong PFS and have better safety, but there is no significant difference in OS
.

Methods The study included patients treated at 152 medical centers in 21 countries.
The included patients were characterized by clear cell or sarcoma-like histology, with measurable lesions, adequate physical status, proper hematology and organ function, and sufficient tumor tissue PD-L1 expression analysis can be performed
.

The patient received atilizumab (1200 mg, IV) + bevacizumab (15 mg/kg, IV) every 3 weeks or received daily oral sunitinib (50 mg) (for 4 consecutive weeks, stop for 2 weeks) )
.

The common primary endpoint was OS in PFS and ITT populations in PD-L1 positive patients
.

Exploratory analysis includes OS, transcriptomics correlation and safety in PD-L1 positive population
.

The tumor tissues (n = 823) of the treated patients were classified by RNA sequencing and OS exploratory analysis was performed
.

Group 1 is anti-angiogenesis/matrix; Group 2 is anti-angiogenesis-related; Group 3 is complement/oxidation; Group 4 is T-effector/proliferation-related; Group 5 is proliferation-related; Group 6 is matrix/proliferation-related; Group 7 For snoRNA
.

Main results: The final analysis of IMmotion151 evaluated 915 patients with metastatic renal cell carcinoma.
The median ages of the tilizumab+bevacizumab and sunitinib groups were 62 and 60 years, respectively
.

In the total population, 669 (73.
1%) patients were male and 246 (26.
9%) patients were female
.

As of the data cutoff on February 14, 2020, the median follow-up time was 40 months, and the median duration of treatment for atilizumab, bevacizumab, and sunitinib were 12.
7 months and 11.
8, respectively Months and 9.
2 months
.

In the final analysis of OS, the incidence of OS events was 55% (504/915).
The median OS of the atelizumab+bevacizumab and sunitinib groups were 36.
1 months and 35.
3 months, respectively (HR=0.
91) ), among the PD-L1 positive population, the median OS of the two treatment groups were 38.
7 months and 31.
6 months (HR=0.
85) (Figure 1)
.

Figure 1 OS final analysis The incidence of treatment-related adverse events of grade 3 to 4 in the combined group was 46%, respectively, and treatment-related adverse events of grade 3 to 4 were proteinuria (8%) (Figure 2)
.

Figure 2 Safety analysis Biomarker analysis Previous transcriptome analysis identified 7 molecular subgroups characterized by different gene expression profiles.
This study reports the correlation between each molecular subgroup and PFS
.

Similar to the PFS results, in the two treatment groups, the OS of the 1 and 2 groups was longer; on the contrary, the OS of the 5 and 6 groups was shorter (Figure 3)
.

Figure 3 Exploratory analysis of the transcriptome correlation of the two treatment groups.
The OS of the sunitinib group 2 group and the combination group 4, 5, and 7 groups was improved (Figure 4)
.

Figure 4 Exploratory analysis of OS in the transcriptome-related subgroups.
Compared with sunitinib, atilizumab + bevacizumab did not significantly improve the OS of patients with newly treated metastatic renal cells
.

However, biomarker analysis provides new perspectives/new ideas for patients receiving different treatments to bring more survival benefits
.

It also provides a new direction for the development of anti-angiogenesis drugs, immunological examination inhibitors and combination therapies
.

References: Robert J.
Motzer, Thomas Powles et al.
Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma.
JAMA Oncol.
doi:10.
1001/jamaoncol .
2021.
5981 Published online December 23, 2021