Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial

Powles, Thomas; Plimack, Elizabeth R.; Soulières, Denis; Waddell, Tom; Stus, V.P.; Gafanov, Rustem; Nosov, Dmitry; Pouliot, Frédéric; Melichar, Bohuslav; Vynnychenko, Ihor; Azevedo, Sérgio Jobim; Borchiellini, Delphine; McDermott, Ray; Bedke, Jens; Tamada, Satoshi; Liu, Yin; Chen, Mei; Molife, L. Rhoda; Atkins, Michael B.; Rini, Brian I.

doi:10.1016/s1470-2045(20)30436-8

Cited by 535 publications

(600 citation statements)

References 18 publications

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“…Interestingly, a post-hoc exploratory analysis of Keynote-426 showed that depth of response (such as >80% tumor reduction but less than complete response) was associated with improvement in overall survival in the pembrolizumab plus axitinib arm, with similar overall survival to the group with complete radiographic response ( 7 ). Additionally, an analysis of depth of response from CheckMate-214 showed similar improvement in overall survival among patients who had a 50–75% tumor reduction as compared with those who had >75% tumor reduction ( 17 ).…”

Section: Discussionmentioning

confidence: 99%

“…FDA has subsequently approved three immunotherapybased first-line combination therapies: ipilimumab plus nivolumab (3), pembrolizumab plus axitinib (4), and avelumab plus axitinib (5). Updated analyses of these phase III trials report RECIST-defined complete radiographic response rates of 11, 9, and 4% with median follow-up of 42, 31, and 13 months respectively (6)(7)(8). Despite these radiographic responses, complete pathologic responses to immunotherapy have rarely been reported.…”

Section: Introductionmentioning

confidence: 99%

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Complete Pathologic Responses With Immunotherapy in Metastatic Renal Cell Carcinoma: Case Reports

et al. 2020

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Immunotherapy-based combinations have become standard of care in advanced renal cell carcinoma (RCC). Despite the potential for complete radiographic response, complete pathologic responses have been rarely reported. We present two cases of confirmed complete pathologic response to immunotherapy despite residual radiographic abnormalities. The first case describes a 68-year-old female with metastatic RCC who was treated with upfront pembrolizumab plus axitinib. She underwent nephrectomy after 15 doses of pembrolizumab with pathology revealing no evidence of viable tumor. To our knowledge, this is the first reported case of a complete pathologic response with pembrolizumab in metastatic RCC. The second case describes a 64-year-old female with metastatic RCC who was treated with second-line nivolumab after progression on cabozantinib. After 13 doses of nivolumab, she underwent nephrectomy with pathology revealing no evidence of viable tumor. These cases highlight the potential for scar tissue, fibrosis, and necrosis to persist radiographically after treatment with immunotherapy despite the absence of viable tumor cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Complete Pathologic Responses With Immunotherapy in Metastatic Renal Cell Carcinoma: Case Reports

et al. 2020

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“…Therefore the combination of pembrolizumab + axitinib was recommended as first-line treatment in the NCCN guidelines (14). However, in the 2020 updated analysis of Keynote-426, in FR patients, the 2-years OS rate was 85.3% and 87.7% for pembrolizumab + axitinib versus sunitinib (HR =1.06, 95% CI, 0.60-1.86, P=0.58), respectively, the median PFS was 20.8 and 18.0 months (HR =0.79, 95% CI, 0.51-1.09, P=0.078) (18). So in FR patients, the survival benefit of combination therapy versus sunitinib is not as obvious as in IR and PR patients.…”

Section: Discussionmentioning

confidence: 97%

Pazopanib in patients with metastatic renal cell carcinoma: a single-center, real-world, retrospective Chinese study

Chen

Jiang

et al. 2021

Transl Androl Urol

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Background: The efficacy and safety of pazopanib in patients diagnosed with metastatic renal cell carcinoma (mRCC) have been demonstrated by a Chinese subgroup analysis of the COMPARZ (Pazopanib Versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma) trial.However, the real-world data are still unknown. This single-center, retrospective study was designed to verify the real-world effects of pazopanib in Chinese patients with mRCC. Methods: Patients with mRCC and a clinical decision to initiate pazopanib as first-line therapy were eligible. The primary endpoint was progression-free survival (PFS), with overall survival (OS), objective response rate (ORR), and safety being evaluated as secondary endpoints. The effectiveness according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk model, number of risk factors in the intermediate risk group, age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and the number and site of organ metastasis were also assessed.Results: A total of 32 patients were enrolled, including 23 (71.9%) males and 9 (28.1%) females. The median age was 57 years (range 29-75 years). With a median follow-up time of 23.8 months, a median PFS of 18.3 months, and an ORR of 37.5%. Median OS was not reached, and the 1-, 2-, and 3-year overall survival rates were 90.6%, 78.1, and 65.6%, respectively. According to IMDC risk model, 37.5% were placed in the favorable risk (FR) subgroup, 56.2% (the majority) were placed in the intermediate risk (IR) subgroup, and 6.3% were placed in the poor risk (PR) subgroup. Compared with the IR and PR groups, the FR group achieved the best ORR (58.3%) and median PFS (22.1 months). Having 1 risk factor, ECOG PS <2, 1 organ metastasis site, and only lung metastasis associated with a higher ORR and better median PFS. The IMDC risk model and number of metastases were associated with PFS. The most common adverse events were change in hair color (69.0%), diarrhea (63%), and hypertension (50%).Conclusions: Pazopanib showed efficacy and safety in real-world Chinese mRCC patients.

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“…Probably the most favorable target for cancer immunotherapy has been the PD-1:PD-L1 pathway. Two anti-PD-1 antibodies (pembrolizumab and nivolumab), and three anti-PD-L1 antibodies (atezolizumab, avelumab and durvalumab) are currently approved for the therapy of several solid tumors [64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83]. Further, several other mAbs against PD-1 and PD-L1 are under clinical development.…”

Section: Pd-l1/pd-1 Axesmentioning

confidence: 99%

Advanced Nanotechnology for Enhancing Immune Checkpoint Blockade Therapy

et al. 2021

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Immune checkpoint receptor signaling pathways constitute a prominent class of “immune synapse,” a cell-to-cell connection that represses T-lymphocyte effector functions. As a possible evolutionary countermeasure against autoimmunity, this strategy is aimed at lowering potential injury to uninfected cells in infected tissues and at minimizing systemic inflammation. Nevertheless, tumors can make use of these strategies to escape immune recognition, and consequently, such mechanisms represent chances for immunotherapy intervention. Recent years have witnessed the advance of pharmaceutical nanotechnology, or nanomedicine, as a possible strategy to ameliorate immunotherapy technical weaknesses thanks to its intrinsic biophysical properties and multifunctional modifying capability. To improve the long-lasting response rate of checkpoint blockade therapy, nanotechnology has been employed at first for the delivery of single checkpoint inhibitors. Further, while therapy via single immune checkpoint blockade determines resistance and a restricted period of response, strong interest has been raised to efficiently deliver immunomodulators targeting different inhibitory pathways or both inhibitory and costimulatory pathways. In this review, the partially explored promise in implementation of nanotechnology to improve the success of immune checkpoint therapy and solve the limitations of single immune checkpoint inhibitors is debated. We first present the fundamental elements of the immune checkpoint pathways and then outline recent promising results of immune checkpoint blockade therapy in combination with nanotechnology delivery systems.

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Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial

Cited by 535 publications

References 18 publications

Complete Pathologic Responses With Immunotherapy in Metastatic Renal Cell Carcinoma: Case Reports

Complete Pathologic Responses With Immunotherapy in Metastatic Renal Cell Carcinoma: Case Reports

Pazopanib in patients with metastatic renal cell carcinoma: a single-center, real-world, retrospective Chinese study

Advanced Nanotechnology for Enhancing Immune Checkpoint Blockade Therapy

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