Dataset Information

Primary Renal Tumour Response in Patients Treated with Nivolumab and Ipilimumab for Metastatic Renal Cell Carcinoma: Real-world Data Assessment.

ABSTRACT: Following CARMENA and SURTIME, patients with metastatic renal cell carcinoma (mRCC) and International Metastatic RCC Database Consortium (IMDC) intermediate and poor risk receive systemic therapy with the primary tumour (primary) in place, with the option of deferred cytoreductive nephrectomy (CN) in responding patients. We retrospectively analysed the safety and efficacy of first-line nivolumab/ipilimumab in 71 primary mRCC patients (42.3% IMDC poor risk; 43.6% with more than three metastatic sites). The baseline mean primary diameter was 9.3 cm and median follow-up was 11.5 mo. Of 69 patients with at least one follow-up computed tomography scan, 23 (33.3 %) had a partial response (PR) of the primary after a median of 4.8 mo, which was associated with a 91.3% overall response rate at metastatic sites (MSs) and absence of progressive disease, irrespective of the IMDC risk. The complete response (CR) rate at MSs (n = 7 [10.1%]) is similar to the CR rate in CheckMate 214. Thirteen deferred CNs were performed (18.8%) after a median of 13 mo, rendering four patients disease free. Only 4.3% of primaries progressed; grade 3-4 immune-related adverse events occurred in 31.9%. Irrespective of the IMDC risk, patients with a PR in the primary had a 1-yr overall survival rate of 89% versus 67% in those without (p = 0.012).

Patient summary

Patients with metastatic kidney cancer receiving immunotherapy with nivolumab and ipilimumab had superior response at metastatic sites and better survival irrespective of International Metastatic RCC Database Consortium (IMDC) risk.

SUBMITTER: Meerveld-Eggink A

PROVIDER: S-EPMC8738899 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionImmune checkpoint inhibitors (ICI) have been approved for front-line therapy in metastatic renal cell carcinoma (mRCC). However, progressive disease often occurs and subsequent therapies are needed. ICI rechallenge may be an option, but there is a lack of data regarding efficacy and prognostic factors. We assessed efficacy of ICI rechallenge and factors associated with better outcomes. Patients and Methods. This ambispective multicenter study included 45 mRCC patients rechallenged with nivolumab ± ipilimumab between 2014 and 2020. Primary endpoint was investigator-assessed best objective response rate (ORR) for ICI rechallenge (ICI-2). Factors associated with ICI-2 progression-free survival (PFS) were evaluated with multivariate Cox models.ResultsORR was 51% (n = 23) at first ICI therapy (ICI-1) and 16% (n = 7) for ICI-2. Median PFS was 11.4 months (95% CI, 9.8-23.5) and 3.5 months (95% CI, 2.8-9.7), and median overall survival was not reached (NR) (95% CI, 37.8-NR) and 24 months (95% CI, 9.9-NR) for ICI-1 and ICI-2, respectively. Factors associated with poorer ICI-2 PFS were a high number of metastatic sites, presence of liver metastases, use of an intervening treatment between ICI regimens, Eastern Cooperative Oncology Group performance status ≥2, and poor International Metastatic RCC Database Consortium score at ICI-2 start. Conversely, ICI-1 PFS >6 months was associated with better ICI-2 PFS. In multivariate analysis, there were only statistical trends toward better ICI-2 PFS in patients with ICI-1 PFS >6 months (p=0.07) and toward poorer ICI-2 PFS in patients who received a treatment between ICI regimens (p=0.07).ConclusionRechallenge with nivolumab-based ICI has some efficacy in mRCC. We identified various prognostic factors in univariate analysis but only statistical trends in multivariate analysis. Our findings bring new evidence on ICI rechallenge and preliminary but unique data that may help clinicians to select patients who will benefit from this strategy.

Project description:BackgroundBone metastases (BM) in renal cell carcinoma (RCC) patients are associated with poor outcomes. There are limited published data on outcomes in these patients with immunotherapy agents. We present a multi-institutional, retrospective analysis of metastatic RCC patients with BM treated with ipilimumab and nivolumab (I + N).ObjectivePatient, tumor, and treatment-related variables were retrospectively collected from electronic medical records of patients with a histologically confirmed diagnosis of RCC and at least one radiographically confirmed BM prior to initiation of I + N. Best objective response was assessed by clinical chart review, imaging reports, and treating physician evaluation; progression-free survival (PFS) and overall survival (OS) were recorded as of 31 December 2020. Descriptive statistics were used to summarize patient characteristics and BM-related variables. Kaplan-Meier method and Mantel-Haenszel log-rank test were used to compare survival among groups. Cox regression univariable and multivariable models were used to correlate patient- and treatment-related variables to outcomes.ResultsEighty patients with RCC and BM treated with I + N were identified. Patients were predominantly male and Caucasian presenting primarily with IMDC intermediate or poor-risk clear-cell RCC. Best response to I + N was progressive disease (46%), stable disease (28%), partial response (21%), and not evaluable (5%). Median PFS was 6.1 months (95% CI 3.8-8.9 months) with the majority of patients (65%) discontinuing I + N due to disease progression. Median OS was 25.6 months (95% CI 14.9-NA) with median follow-up of 25.2 months. A multivariable regression model for PFS showed several variables to be significantly associated with worse PFS including female gender [p = 0.02; hazard ratio (HR) 2.16; 95% CI 1.14-4.12], metastases to other sites (p = 0.006; HR 2.12; 95% CI 1.24-3.62) and presence of BM to ribs (p = 0.0007; HR 2.61; 95% CI 1.50-4.52). A multivariable Cox model of OS showed no prior radiation therapy to BM (p = 0.02; HR 2.17; 95% CI 1.13-4.17) and presence of liver metastases (p = 0.0006; HR 3.19; 95% CI 1.65-6.19) to be significantly associated with worse OS.ConclusionRCC patients with ≥ 1 BM who received I + N therapy had a relatively low response rate, PFS, and OS. Strategies to improve outcomes in this subset of patients are needed.

Project description:PurposeCheckMate 032 is an open-label, multicohort study that includes patients with unresectable locally advanced or metastatic urothelial carcinoma (mUC) treated with nivolumab 3 mg/kg monotherapy every 2 weeks (NIVO3), nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks (NIVO3+IPI1), or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks (NIVO1+IPI3). We report on the expanded NIVO1+IPI3 cohort and extended follow-up for the NIVO3 and NIVO3+IPI1 cohorts.MethodsPatients with platinum-pretreated mUC were enrolled in this phase I/II multicenter study to receive NIVO3, NIVO3+IPI1, or NIVO1+IPI3 until disease progression or unacceptable toxicity. Primary end point was investigator-assessed objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, including duration of response.ResultsSeventy-eight patients were treated with NIVO3 (minimum follow-up, 37.7 months), 104 with NIVO3+IPI1 (minimum follow-up, 38.8 months), and 92 with NIVO1+IPI3 (minimum follow-up, 7.9 months). Objective response rate was 25.6%, 26.9%, and 38.0% in the NIVO3, NIVO3+IPI1, and NIVO1+IPI3 arms, respectively. Median duration of response was more than 22 months in all arms. Grade 3 or 4 treatment-related adverse events occurred in 21 (26.9%), 32 (30.8%), and 36 (39.1%) patients treated with NIVO3, NIVO3+IPI1, and NIVO1+IPI3, respectively. Grade 5 treatment-related pneumonitis occurred in one patient each in the NIVO3 and NIVO3+IPI1 arms.ConclusionWith longer follow-up, NIVO3 demonstrated sustained antitumor activity alone and in combination with ipilimumab. NIVO1+IPI3 provided the greatest antitumor activity of all regimens, with a manageable safety profile. This result not only supports additional study of NIVO1+IPI3 in mUC, but demonstrates the potential benefit of immunotherapy combinations in this disease.

Project description:ImportanceRecently, new drugs have been approved for the first-line treatment of metastatic renal cell carcinoma (mRCC). Nivolumab plus ipilimumab significantly increases overall survival for intermediate- and poor-risk patients with mRCC. However, considering the high cost of nivolumab plus ipilimumab, there is a need to assess its value by considering both efficacy and cost.ObjectiveTo evaluate the cost-effectiveness of nivolumab plus ipilimumab vs sunitinib in the first-line setting for intermediate- and poor-risk patients with mRCC from the US payer perspective.Design, setting, and participantsA Markov model was developed to compare the lifetime cost and effectiveness of nivolumab plus ipilimumab vs sunitinib in the first-line treatment of mRCC using outcomes data from the CheckMate 214 phase 3 randomized clinical trial, which included 1096 patients with mRCC (median age, 62 years) and compared nivolumab plus ipilimumab vs sunitinib as first-line treatment of mRCC. In the analysis, patients were modeled to receive sunitinib or nivolumab plus ipilimumab for 4 doses followed by nivolumab monotherapy.Main outcomes and measuresLife-years, quality-adjusted life-years (QALYs), and lifetime costs were estimated, at a willingness-to-pay threshold of $100 000 to $150 000 per QALY. Univariable, 2-way, and probabilistic sensitivity analyses were performed to evaluate the model uncertainty. Additional subgroup analyses were performed.ResultsNivolumab plus ipilimumab provided an additional 0.96 QALYs, at a cost of $108 363 per QALY. Sensitivity analyses found the results to be most sensitive to overall survival hazard ratio (0.63; 95% CI, 0.44-0.89) and mean patient weight (70 kg, range, 40-200 kg). Other variables, such as the cost of nivolumab plus ipilimumab (mean, $32 213.44; range, $25 770.75-$38 656.13), utility values for nivolumab plus ipilimumab (mean, 0.82; range, 0.65-0.98), and proportion receiving nivolumab in sunitinib arm (mean, 0.27; range, 0.22-0.32), had a moderate or minor influence on model results. Subgroup analyses demonstrated that nivolumab plus ipilimumab was most cost-effective for patients with programmed cell death 1 ligand 1 expression of at least 1% ($86 390 per QALY).Conclusions and relevanceIn this model, nivolumab plus ipilimumab was estimated to be cost-effective compared with sunitinib for intermediate- and poor-risk patients with mRCC at a willingness-to-pay threshold from $100 000 to $150 000 per QALY.

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Primary Renal Tumour Response in Patients Treated with Nivolumab and Ipilimumab for Metastatic Renal Cell Carcinoma: Real-world Data Assessment.

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