BPI20-012: Relative Risk of Various Endocrinopathies Associated With the Use of Immune Checkpoint Inhibitors in the First-Line Treatment of Advanced Renal Cell Carcinoma: a Systematic Review and Meta-Analysis

675 Background: Sunitinib was the standard first-line treatment of advanced renal cell carcinoma (aRCC) for the past decade, but it has been associated with significant hematological toxicities. Immune checkpoint inhibitors (ICI) based regimens have become the new preferred treatment for aRCC in the first-line setting. We conducted a meta-analysis of phase 3 randomized controlled trials (RCTs) to determine the relative risk of hematological toxicities associated with upfront use of ICI-based regimens for aRCC. Methods: We conducted a systematic search at PUBMED, MEDLINE, EMBASE, and meeting abstracts as per PRISMA guidelines from inception until May 2019. Phase 3 RCTs using ICIs in the intervention arm for the first-line treatment of aRCC were included. We used the Mantel-Haenszel (MH) method utilizing random effects model to calculate pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested with I2 value. Results: Four phase 3 RCTs, CheckMate 214, IMmotion151, JAVELIN Renal 101 and KEYNOTE-426, randomizing 3706 patients were included in the analysis of anemia and thrombocytopenia. CheckMate 214 did not report the number of neutropenia. Hence, other 3 RCTs that included 2624 patients were analyzed for neutropenia. Following regimens were used in the study arms — CheckMate 214: nivolumab+ipilimumab, IMmotion151: atezolizumab+bevacizumab, JAVELIN Renal 101: axitinib+avelumab; and KEYNOTE-426: axitinib+ pembrolizumab. Sunitinib was used in the control arms for all the studies. The pooled RR of any-grade hematological toxicities are as follows — anemia: 0.31 (95% CI:0.24-0.41, P< 0.00001, I2=39%); thrombocytopenia: 0.11 (95% CI: 0.06-0.19, P<0.00001, I2=63%); neutropenia: 0.08 (95% CI: 0.05-0.13, P<0.00001, I2=0%). The pooled RR of grade 3 and higher hematological toxicities are as follows — anemia: 0.14 (95% CI:0.08-0.25, P< 0.00001, I2=0); thrombocytopenia: 0.06 (95% CI:0.02-0.16, P<0.00001, I2=4%); neutropenia: 0.06 (95% CI: 0.02-0.16, P<0.00001, I2=0%). Conclusions: ICI-based regimens have significantly reduced risk of any-grade as well as high-grade hematological toxicities compared to sunitinib in patients with aRCC.

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Relative risk of pneumonitis associated with first-line use of immune checkpoint inhibitors in advanced renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.676 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 676-676

Author(s):

Nusrat Jahan ◽

Francis Mogollon-Duffo ◽

Srikala Meda ◽

Fred L. Hardwicke ◽

Lukman Aderoju Tijani

Keyword(s):

Renal Cell Carcinoma ◽

Relative Risk ◽

Immune Checkpoint ◽

Renal Cell ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Line Treatment ◽

First Line ◽

Phase 3 ◽

First Line Treatment

676 Background: After approval in 2006, sunitinib remained the standard for the first line treatment of advanced renal cell carcinoma (aRCC) for a decade. Immune checkpoint inhibitors (ICI) have changed the landscape of aRCC management in recent years. Pneumonitis is a significant immune related adverse event (iRAE) associated with ICIs causing morbidity, mortality and treatment interruption. We conducted a meta-analysis of phase 3 randomized controlled trials (RCTs) to determine the relative risk of pneumonitis associated with first line use of ICIs for aRCCs. Methods: We conducted a systematic search using PUBMED, MEDLINE, EMBASE, and meeting abstracts as per PRISMA guidelines from inception until May 2019. Phase 3 RCTs using ICIs in the intervention arm for the first line treatment of aRCC and reporting the number of pneumonitis for both intervention and control arms were included in the analysis. We used the Mantel-Haenszel (MH) method utilizing random effects model to calculate pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested with I2 value. Results: Three phase 3 RCTs, CheckMate 214, IMmotion151 and KEYNOTE-426, randomizing 2833 patients (1427 in the ICI arms and 1406 in the control arms) were included in the analysis. ICI regimens used in the study arms were as follows — CheckMate 214: nivolumab and ipilimumab, IMmotion151: atezolizumab and bevacizumab, and KEYNOTE-426: pembrolizumab and axitinib. Sunitinib was used for all the control arms. Randomization was 1:1 in all three studies. Pneumonitis of any-grade was reported in 56 (3.92%) patients in the ICI arms versus 1 (0.07%) patient in the control arms. The pooled RR of any grade pneumonitis was 22.11 (95% CI: 5.34-91.55, P<0.0001, I2=0%). Grade 3 and above pneumonitis was reported in 12 (0.84%) patients in the ICI arms versus 0 (0%) patient in the control arms with pooled RR of 8.39 (95% CI: 1.54-45.80, P=0.01, I2=0%). Conclusions: The relative risk of any-grade as well as high-grade pneumonitis are significantly higher with ICI based regimens compared to sunitinib for aRCC. Early detection and prompt intervention are vital to reduce morbidy and mortality associated with this iRAE.

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