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Pazopanib versus sunitinib in Chinese patients with locally advanced or metastatic renal cell carcinoma: pooled subgroup analysis from the randomized, COMPARZ studies.

ABSTRACT: BACKGROUND:We performed a pooled analysis of the COMPARZ study assessing efficacy and safety of pazopanib versus sunitinib in treatment-naïve Chinese patients with locally advanced and/or metastatic renal cell carcinoma (a/mRCC). METHODS:In the COMPARZ study, patients were randomized (1:1) to receive pazopanib 800?mg once daily (QD) continuously or sunitinib 50?mg QD in 6-week?cycles (4?weeks on, 2?weeks off). The primary endpoint was progression-free survival (PFS); secondary endpoints included overall response rate (ORR), overall survival (OS), and safety. PFS and ORR were assessed by independent review committee (IRC) and local investigators. RESULTS:Of the 209 Chinese patients (pazopanib, [n?=?109] and sunitinib, [n?=?100]), 155 (74%) were males and median age was 57?years (range, 18-79). Median PFS was 13.9?months for pazopanib versus 14.3?months for sunitinib per investigator assessment and 8.3?months in both arms per IRC assessment; PFS hazard ratio was 1.17 (investigator) and 0.99 (IRC). Median OS was not reached in pazopanib arm and was 29.5?months in sunitinib arm. ORR was significantly higher in pazopanib arm versus sunitinib arm (investigator: 41% versus 23% [P?=?0.0052]; IRC: 35% versus 20% [P?=?0.0203]). Pazopanib was generally well tolerated in Chinese patients with a/mRCC. Most frequent AEs in the pazopanib arm were diarrhea and hair color changes whereas the most frequent AEs in the sunitinib arm were decreased platelets, decreased neutrophil count, and thrombocytopenia. CONCLUSION:The results of the pooled analysis were consistent with the overall population in the COMPARZ study, and confirmed similar PFS and OS of pazopanib and sunitinib in the Chinese patients. TRIAL REGISTRATION:clinical trials.gov, NCT00720941 (August 14, 2008) and NCT01147822 (May 19, 2010).

SUBMITTER: Sheng X

PROVIDER: S-EPMC7071746 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Pazopanib versus sunitinib in Chinese patients with locally advanced or metastatic renal cell carcinoma: pooled subgroup analysis from the randomized, COMPARZ studies.

Sheng Xinan X Jin Jie J He Zhisong Z Huang Yiran Y Zhou Aiping A Wang Jinwan J Ren Xiubao X Ye Dingwei D Zhang Xu X Qin Shukui S Zhou Fangjian F Wang Binhui B Guo Jun J

BMC cancer 20200314 1

<h4>Background</h4>We performed a pooled analysis of the COMPARZ study assessing efficacy and safety of pazopanib versus sunitinib in treatment-naïve Chinese patients with locally advanced and/or metastatic renal cell carcinoma (a/mRCC).<h4>Methods</h4>In the COMPARZ study, patients were randomized (1:1) to receive pazopanib 800 mg once daily (QD) continuously or sunitinib 50 mg QD in 6-week cycles (4 weeks on, 2 weeks off). The primary endpoint was progression-free survival (PFS); secondary end ...[more]

PMID: 32171288

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Project description:BackgroundSunitinib and pazopanib are the only two targeted therapies for the first-line treatment of locally advanced or metastatic renal cell carcinoma (mRCC) recommended by the United Kingdom's National Institute for Health and Care Excellence. Pazopanib demonstrated non-inferior efficacy and a differentiated safety profile versus sunitinib in the phase III COMPARZ trial. The current analysis provides a direct comparison of the cost-effectiveness of pazopanib versus sunitinib from the perspective of the United Kingdom's National Health Service based on data from COMPARZ and other sources.MethodsA partitioned-survival analysis model with three health states (alive with no progression, alive with progression, or dead) was used to estimate the incremental cost per quality-adjusted life-year (QALY) gained for pazopanib versus sunitinib over five years (duration of follow-up for final survival analysis in COMPARZ). The proportion of patients in each health state over time was based on Kaplan-Meier distributions for progression-free and overall survival from COMPARZ. Utility values were based on EQ-5D data from the pivotal study of pazopanib versus placebo. Costs were based on medical resource utilisation data from COMPARZ and unit costs from secondary sources. Probabilistic and deterministic sensitivity analyses were conducted to assess uncertainty of model results.ResultsIn the base case, pazopanib was estimated to provide more QALYs (0.0565, 95% credible interval [CrI]: -0.0920 to 0.2126) at a lower cost (-£1,061, 95% CrI: -£4,328 to £2,067) versus sunitinib. The probability that pazopanib yields more QALYs than sunitinib was estimated to be 76%. For a threshold value of £30,000 per QALY gained, the probability that pazopanib is cost-effective versus sunitinib was estimated to be 95%. Pazopanib was dominant in most scenarios examined in deterministic sensitivity analyses.ConclusionsPazopanib is likely to be a cost-effective treatment option compared with sunitinib as first-line treatment of mRCC in the United Kingdom.

Project description:BackgroundCurrent first-line treatments for metastatic renal cell carcinoma (mRCC) include the multityrosine kinase inhibitors pazopanib and sunitinib. Both agents had similar progression-free survival (PFS) and overall survival (OS) in the COMPARZ trial (Comparing the Efficacy, Safety and Tolerability of Pazopanib versus Sunitinib); however, the adverse event profiles of the 2 agents are different. In the PISCES trial (Patient Preference Study of Pazopanib versus Sunitinib in Advanced or Metastatic Kidney Cancer), patients and physicians preferred pazopanib primarily because it offered better health-related quality of life (HRQoL) and caused less fatigue.ObjectiveTo compare the cost-effectiveness of pazopanib versus sunitinib from a U.S. health care system perspective in the first-line treatment of patients with mRCC.MethodsA partitioned-survival analysis model with 3 health states (preprogression, postprogression, and dead), data from 2 randomized controlled trials of pazopanib versus sunitinib (COMPARZ and PISCES), and secondary sources were used to calculate the incremental cost per quality-adjusted life-year (QALY) gained for pazopanib versus sunitinib. A time horizon of 37.5 months was used in the base case, consistent with the duration of follow-up used in the COMPARZ trial. The proportion of patients in each health state over time was based on Kaplan-Meier survival distributions for PFS and OS from the COMPARZ trial. Utility values were obtained from the PISCES trial. Costs were based on medical resource utilization data from the COMPARZ trial and unit costs from secondary sources. Probabilistic sensitivity analyses and deterministic sensitivity analyses were conducted.ResultsIn the base case, pazopanib was estimated to provide more QALYs at a lower cost compared with sunitinib (pazopanib dominant). In probabilistic sensitivity analyses, pazopanib was projected to be dominant in 69% of the simulations. The probability that pazopanib was more cost-effective than sunitinib was ≥ 90% for threshold values of cost-effectiveness between the range of $10,000-$160,000 per QALY gained. In deterministic sensitivity analyses, pazopanib was dominant in all scenarios examined.ConclusionResults of this study suggest that pazopanib is cost-effective compared with sunitinib as the first-line treatment of patients with mRCC in the United States.

Project description:BackgroundIn Canada and elsewhere, pazopanib and sunitinib-tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptors-are recommended as first-line treatment for patients with metastatic renal cell carcinoma (mrcc). A large randomized noninferiority trial of pazopanib versus sunitinib (comparz) demonstrated that the two drugs have similar efficacy; however, patients randomized to pazopanib experienced better health-related quality of life (hrqol) and nominally lower rates of non-study medical resource utilization.MethodsThe cost-effectiveness of pazopanib compared with sunitinib for first-line treatment of mrcc from a Canadian health care system perspective was evaluated using a partitioned-survival model that incorporated data from comparz and other secondary sources. The time horizon of 5 years was based on the maximum duration of follow-up in the final analysis of overall survival from the comparz trial. Analyses were conducted first using list prices for pazopanib and sunitinib and then by assuming that the prices of sunitinib and pazopanib would be equivalent.ResultsBased on list prices, expected costs were CA$10,293 less with pazopanib than with sunitinib. Pazopanib was estimated to yield 0.059 more quality-adjusted life-years (qalys). Pazopanib was therefore dominant (more qalys and lower costs) compared with sunitinib in the base case. In probabilistic sensitivity analyses, pazopanib was dominant in 79% of simulations and was cost-effective in 90%-100% of simulations at a threshold cost-effectiveness ratio of CA$100,000. Assuming equivalent pricing, pazopanib yielded CA$917 in savings in the base case, was dominant in 36% of probabilistic sensitivity analysis simulations, and was cost-effective in 89% of simulations at a threshold cost-effectiveness ratio of CA$100,000.ConclusionsCompared with sunitinib, pazopanib is likely to be a cost-effective option for first-line treatment of mrcc from a Canadian health care perspective.

Project description:BackgroundCombination treatment with immune checkpoint inhibitors and antiangiogenic drugs has shown encouraging preliminary antitumor activity across various tumor types including advanced or metastatic renal cell carcinoma (aRCC). The open-label, parallel-cohort, dose-escalation, phase I CheckMate 016 study evaluated the efficacy and safety of nivolumab in combination with antiangiogenic tyrosine kinase inhibitors or ipilimumab. Long-term outcomes from this study for the combination of nivolumab plus sunitinib or pazopanib in aRCC are presented.MethodsPatients with aRCC received nivolumab plus either sunitinib (50 mg/day, 4 weeks on/2 weeks off; N + S) or pazopanib (800 mg/day; N + P) until progression/unacceptable toxicity. The nivolumab starting dose was 2 mg/kg every 3 weeks, with planned escalation to 5 mg/kg every 3 weeks. Primary endpoints were safety and tolerability; antitumor activity was a secondary endpoint.ResultsArm N + S enrolled 33 patients, 19 of whom were treatment-naïve; this arm advanced to the expansion phase. Median follow-up was 50.0 months. Patients experienced high frequencies of adverse events (AEs) including treatment-related AEs (100%), grade 3/4 treatment-related AEs (82%), and treatment-related AEs leading to discontinuation (39%). Investigator-assessed objective response rate (ORR) was 55% (18/33) and median progression-free survival (PFS) was 12.7 months. Median overall survival (OS) was not reached. Arm N + P enrolled 20 patients, all had ≥1 prior systemic therapy; this arm was closed due to dose-limiting toxicities and did not proceed to expansion. Median follow-up was 27.1 months. Patients treated with N + P experienced high frequencies of AEs including treatment-related AEs (100%), grade 3/4 treatment-related AEs (70%), and treatment-related AEs leading to discontinuation (25%). Investigator-assessed ORR was 45% (9/20) and median PFS was 7.2 months. Median OS was 27.9 months.ConclusionsThe addition of standard doses of sunitinib or pazopanib to nivolumab resulted in a high incidence of high-grade toxicities limiting future development of either combination regimen. While there was no adverse impact on response and the OS outcome was notable, the findings suggest that the success of combination regimens based on immune checkpoint inhibitors and antiangiogenic drugs may be dependent on careful selection of the antiangiogenic component and dose.Trial registrationClinicaltrials.gov identifier: NCT01472081 . Registered 16 November 2011.

Project description:BackgroundWe report updated data for avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma from the third interim analysis of the phase III JAVELIN Renal 101 trial.Patients and methodsProgression-free survival (PFS), objective response rate (ORR), and duration of response per investigator assessment (RECIST version 1.1) and overall survival (OS) were evaluated in the overall population and in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups; safety was also assessed.ResultsOverall, median OS [95% confidence interval (CI)] was not reached [42.2 months-not estimable (NE)] with avelumab plus axitinib versus 37.8 months (31.4-NE) with sunitinib [hazard ratio (HR) 0.79, 95% CI 0.643-0.969; one-sided P = 0.0116], and median PFS (95% CI) was 13.9 months (11.1-16.6 months) versus 8.5 months (8.2-9.7 months), respectively (HR 0.67, 95% CI 0.568-0.785; one-sided P < 0.0001). In patients with IMDC favorable-, intermediate-, poor-, or intermediate plus poor-risk disease, respectively, HRs (95% CI) for OS with avelumab plus axitinib versus sunitinib were 0.66 (0.356-1.223), 0.84 (0.649-1.084), 0.60 (0.399-0.912), and 0.79 (0.636-0.983), and HRs (95% CIs) for PFS were 0.71 (0.490-1.016), 0.71 (0.578-0.866), 0.45 (0.304-0.678), and 0.66 (0.550-0.787), respectively. ORRs, complete response rates, and durations of response favored avelumab plus axitinib overall and across all risk groups. In the avelumab plus axitinib arm, 81.1% had a grade ≥3 treatment-emergent adverse event (TEAE), and incidences of TEAEs and immune-related AEs were highest <6 months after randomization.ConclusionsAvelumab plus axitinib continues to show improved efficacy versus sunitinib and a tolerable safety profile overall and across IMDC risk groups. The OS trend favors avelumab plus axitinib versus sunitinib, but data remain immature; follow-up is ongoing.Trial registrationClinicalTrials.govNCT02684006; https://clinicaltrials.gov/ct2/show/NCT02684006.

Project description:BackgroundIn a single-group, phase 1b trial, avelumab plus axitinib resulted in objective responses in patients with advanced renal-cell carcinoma. This phase 3 trial involving previously untreated patients with advanced renal-cell carcinoma compared avelumab plus axitinib with the standard-of-care sunitinib.MethodsWe randomly assigned patients in a 1:1 ratio to receive avelumab (10 mg per kilogram of body weight) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were progression-free survival and overall survival among patients with programmed death ligand 1 (PD-L1)-positive tumors. A key secondary end point was progression-free survival in the overall population; other end points included objective response and safety.ResultsA total of 886 patients were assigned to receive avelumab plus axitinib (442 patients) or sunitinib (444 patients). Among the 560 patients with PD-L1-positive tumors (63.2%), the median progression-free survival was 13.8 months with avelumab plus axitinib, as compared with 7.2 months with sunitinib (hazard ratio for disease progression or death, 0.61; 95% confidence interval [CI], 0.47 to 0.79; P<0.001); in the overall population, the median progression-free survival was 13.8 months, as compared with 8.4 months (hazard ratio, 0.69; 95% CI, 0.56 to 0.84; P<0.001). Among the patients with PD-L1-positive tumors, the objective response rate was 55.2% with avelumab plus axitinib and 25.5% with sunitinib; at a median follow-up for overall survival of 11.6 months and 10.7 months in the two groups, 37 patients and 44 patients had died, respectively. Adverse events during treatment occurred in 99.5% of patients in the avelumab-plus-axitinib group and in 99.3% of patients in the sunitinib group; these events were grade 3 or higher in 71.2% and 71.5% of the patients in the respective groups.ConclusionsProgression-free survival was significantly longer with avelumab plus axitinib than with sunitinib among patients who received these agents as first-line treatment for advanced renal-cell carcinoma. (Funded by Pfizer and Merck [Darmstadt, Germany]; JAVELIN Renal 101 ClinicalTrials.gov number, NCT02684006.).

Project description:BackgroundNivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study. This phase 3 trial compared nivolumab plus ipilimumab with sunitinib for previously untreated clear-cell advanced renal-cell carcinoma.MethodsWe randomly assigned adults in a 1:1 ratio to receive either nivolumab (3 mg per kilogram of body weight) plus ipilimumab (1 mg per kilogram) intravenously every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks, or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The coprimary end points were overall survival (alpha level, 0.04), objective response rate (alpha level, 0.001), and progression-free survival (alpha level, 0.009) among patients with intermediate or poor prognostic risk.ResultsA total of 1096 patients were assigned to receive nivolumab plus ipilimumab (550 patients) or sunitinib (546 patients); 425 and 422, respectively, had intermediate or poor risk. At a median follow-up of 25.2 months in intermediate- and poor-risk patients, the 18-month overall survival rate was 75% (95% confidence interval [CI], 70 to 78) with nivolumab plus ipilimumab and 60% (95% CI, 55 to 65) with sunitinib; the median overall survival was not reached with nivolumab plus ipilimumab versus 26.0 months with sunitinib (hazard ratio for death, 0.63; P<0.001). The objective response rate was 42% versus 27% (P<0.001), and the complete response rate was 9% versus 1%. The median progression-free survival was 11.6 months and 8.4 months, respectively (hazard ratio for disease progression or death, 0.82; P=0.03, not significant per the prespecified 0.009 threshold). Treatment-related adverse events occurred in 509 of 547 patients (93%) in the nivolumab-plus-ipilimumab group and 521 of 535 patients (97%) in the sunitinib group; grade 3 or 4 events occurred in 250 patients (46%) and 335 patients (63%), respectively. Treatment-related adverse events leading to discontinuation occurred in 22% and 12% of the patients in the respective groups.ConclusionsOverall survival and objective response rates were significantly higher with nivolumab plus ipilimumab than with sunitinib among intermediate- and poor-risk patients with previously untreated advanced renal-cell carcinoma. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 214 ClinicalTrials.gov number, NCT02231749 .).

Dataset Information

Pazopanib versus sunitinib in Chinese patients with locally advanced or metastatic renal cell carcinoma: pooled subgroup analysis from the randomized, COMPARZ studies.

Publications

Pazopanib versus sunitinib in Chinese patients with locally advanced or metastatic renal cell carcinoma: pooled subgroup analysis from the randomized, COMPARZ studies.

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