IMmotion151: A Randomized Phase III Study of Atezolizumab Plus Bevacizumab vs Sunitinib in Untreated Metastatic Renal Cell Carcinoma (mRCC)

Motzer, Robert J.; Powles, Thomas; Atkins, Michael B.; Escudier, Bernard; McDermott, David F.; Suárez, Cristina; Bracarda, Sergio; Stadler, Walter M.; Donskov, Frede; Lee, Jae‐Lyun; Hawkins, Robert E.; Ravaud, Alain; Alekseev, B. Ya.; Staehler, Michael; Uemura, Mamoru; Donaldson, Francis; Li, Shi; Huseni, Mahrukh; Schiff, Christina; Rini, Brian I.

doi:10.1200/jco.2018.36.6_suppl.578

Cited by 186 publications

(145 citation statements)

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“…5,6 In patients with PD-L1-positive mRCC who are treated in the first-line setting, the IMmotion 150 phase 2 trial reported an HR of 0.64 (P = .095) for a progression-free survival benefit in favor of atezolizumab (a PD-L1 inhibitor) plus bevacizumab (a VEGF inhibitor) compared with sunitinib. 8 Patients with PD-L1-positive disease were reported to achieve an ORR of 43% with the combination of atezolizumab and bevacizumab versus 35% with sunitinib. 8 Patients with PD-L1-positive disease were reported to achieve an ORR of 43% with the combination of atezolizumab and bevacizumab versus 35% with sunitinib.…”

Section: Introductionmentioning

confidence: 99%

“…8 Patients with PD-L1-positive disease were reported to achieve an ORR of 43% with the combination of atezolizumab and bevacizumab versus 35% with sunitinib. 8 To the best of our knowledge, outcomes and prognostic tools have yet to be clearly defined in patients with mRCC who are treated with IO checkpoint inhibitors. 8 To the best of our knowledge, outcomes and prognostic tools have yet to be clearly defined in patients with mRCC who are treated with IO checkpoint inhibitors.…”

Section: Introductionmentioning

confidence: 99%

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Checkpoint inhibitors in patients with metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

Yip¹,

Wells²,

Moreira³

et al. 2018

Cancer

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BACKGROUND:To the authors' knowledge, outcomes and prognostic tools have yet to be clearly defined in patients with metastatic renal cell carcinoma (mRCC) who are treated with immuno-oncology (IO) checkpoint inhibitors (programmed death-ligand 1 [PD-L1] inhibitors). In the current study, the authors aimed to establish IO efficacy benchmarks in patients with mRCC and update patient outcomes in each International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic class. METHODS: A retrospective analysis was performed using the IMDC database with data from 38 centers. It included patients with mRCC who were treated with ≥1 line of IO. Overall response rates (ORRs), duration of treatment (DOT), and overall survival (OS) were calculated. Patients were stratified using IMDC prognostic factors. RESULTS: A total of 687 patients (90% with clear cell and 10% with non-clear cell) were included. The ORR was 27% in evaluable patients (461 patients). In patients treated with first-line nivolumab and ipilimumab (49 patients), the combination of PD-L1 inhibitor and vascular endothelial growth factor inhibitor (72 patients), and PD-L1 inhibitor (51 patients), the ORR was 31%, 39%, and 40%, respectively, and the median DOT was 8.3 months, 14.7 months, and 8.3 months, respectively. The ORR for second-line, third-line, and fourth-line nivolumab was 22%, 24%, and 26%, respectively. The median DOT was 5.7 months, 6.2 months, and 8.3 months, respectively, in the second-line, third-line, and fourth-line settings. When segregated into IMDC favorable-risk, intermediate-risk, and poor-risk groups, the median OS rates for the first-line, second-line, third-line, and fourth-line treatment settings were not reached (NR), NR, and NR, respectively (P = .163); NR, 26.7 months, and 7.4 months, respectively (P < 0. 0001); 36.1 months, 28.2 months, and 11.1 months, respectively (P = .016); and NR, NR, and 6.7 months, respectively (P = .047). CONCLUSIONS: The ORR was not found to deteriorate from the first-line to the fourth-line of IO therapy. In the second line through fourth line, the IMDC criteria appropriately stratified patients into favorable-risk, intermediate-risk, and poor-risk groups for OS. Cancer 2018;124:3677-3683.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Checkpoint inhibitors in patients with metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

Yip¹,

Wells²,

Moreira³

et al. 2018

Cancer

Self Cite

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“…We included nine RCTs and we identified another eight potentially relevant RCTs. Table shows identifiers and references of the nine included RCTs: TroVax Renal Immunotherapy Survival Trial, AVOREN, Global Advanced Renal‐Cell Carcinoma Trial, Sunitinib compared with interferon alfa, CheckMate 025, CheckMate 214, TORAVA, CALGB‐90206, and IMPRINT, Table shows also identifiers and references of the eight potentially relevant ongoing RCTs: JAVELIN Renal 101, ADAPT, IMmotion150, IMmotion151, Keynote‐426,Keynote‐581, CheckMate 800, and CheckMate 9ER.…”

Section: Resultsmentioning

confidence: 99%

Immunotherapy for metastatic renal cell carcinoma: A systematic review

Peinemann

Unverzagt

Hadjinicolaou

et al. 2019

J Evidence Based Medicine

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Background Various approaches have been developed for the treatment of metastatic renal cell carcinoma (MRCC). The objective was to assess the efficacy of immunotherapeutic approaches. Methods We included participants diagnosed with all types of histologically confirmed MRCC, the test intervention was immunotherapy alone or combined with other immunotherapy or targeted therapies, and the study design was restricted to randomized controlled trials (RCTs). Primary outcomes were overall survival, adverse events, and health‐related quality of life. We conducted the last search in March 31, 2018. Results We included nine RCTs, and we established seven different treatment comparisons according to the type of data. Two RCTs favored nivolumab as monotherapy or combined with ipilimumab on account of all primary outcomes. The efficacy data of all other comparisons were either indifferent or favored the control group. Conclusion The immune checkpoint inhibitors nivolumab as monotherapy or combined with ipilimumab appears to be the only new immunotherapy that may improve overall survival in participants with metastatic renal cell carcinoma. Interferon‐α alone is unfavorable to targeted therapies with respect to overall survival and adverse events.

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“…Similarly, a phase 2 study of bevacizumab and high-dose interferon-α2b in metastatic melanoma reported a response rate of 24% 27 . More recently, PD-L1 blockade with atezolizumab in combination with VEGF inhibition with bevacizumab has shown promising activity in phase II-III trial testing in metastatic renal cell carcinoma (mRCC) supporting the use of atezolizumab + bevacizumab as a first line treatment option in mRCC 28 . This phase III data in mRCC is consistent with our data in this study and support a role for VEGF inhibition as an important component of a combination immunotherapeutic strategy.…”

Section: Discussionmentioning

confidence: 99%

NCI 8628: A randomized phase 2 study of ziv‐aflibercept and high‐dose interleukin 2 or high‐dose interleukin 2 alone for inoperable stage III or IV melanoma

Tarhini

Frankel

Ruel

et al. 2018

Cancer

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BACKGROUND Interleukin-2 (IL2) is a growth factor for T and NK cells, promotes pro-inflammatory cytokines and can lead to durable responses in melanoma. VEGF promotes angiogenesis and modulates host innate and adaptive immunity. High VEGF levels were associated with nonresponse to IL2. Ziv- aflibercept may deplete VEGF and thereby enhance antitumor T cell responses, supporting a combination immunotherapeutic strategy with IL2. METHODS NCI 8628 was a phase II trial of ziv-aflibercept and IL2 (arm A) versus IL2 alone (arm B) randomized 2:1 respectively. Eligible patients had inoperable Stage III or IV melanoma. The primary endpoint was progression-free survival (PFS). RESULTS 89 patients were enrolled and 84 treated. Median follow up was 41.4 months. Among treated patients (55 in A, 29 in B), PFS was significantly improved in favor of A: median (95% CI) of 6.9 (4.1–8.7) months versus 2.3 (1.6–3.5) months, p <0.001. No significant difference in OS: median (95% CI) of 26.9 (14.4–63.6) months (A) and 24.2 (11.3–36.4) months (B). Response rate (RECIST) was 22% in A (4CR, 8PR) and 17% in B (1CR, 4PR). Stable disease or PR or CR was seen in 65% in A and 48% in B. The combination was superior to monotherapy in patients with high and low levels of serum VEGF and VEGFR2. Adverse events were consistent with the expected profiles of monotherapy with IL2 and ziv- aflibercept. CONCLUSION Ziv-aflibercept and IL2 significantly improved PFS over IL2 alone, meeting the study’s primary endpoint. Our findings support further study of immunotherapeutic combination strategies involving VEGF inhibitors.

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IMmotion151: A Randomized Phase III Study of Atezolizumab Plus Bevacizumab vs Sunitinib in Untreated Metastatic Renal Cell Carcinoma (mRCC)

Cited by 186 publications

References 0 publications

Checkpoint inhibitors in patients with metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

Checkpoint inhibitors in patients with metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

Immunotherapy for metastatic renal cell carcinoma: A systematic review

NCI 8628: A randomized phase 2 study of ziv‐aflibercept and high‐dose interleukin 2 or high‐dose interleukin 2 alone for inoperable stage III or IV melanoma

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