Nivolumab plus ipilimumab in patients with advanced non-clear cell renal cell carcinoma (nccRCC): Safety and efficacy from CheckMate 920.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 309-309
Author(s):  
Scott S. Tykodi ◽  
Lucio N. Gordan ◽  
Robert S. Alter ◽  
Edward Arrowsmith ◽  
Michael Roger Harrison ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Renal Cell ◽  
Clear Cell ◽  
Karnofsky Performance Status ◽  
Collecting Duct ◽  
Performance Status ◽  
Objective Response ◽  
Phase Iii ◽  
Safety And Efficacy ◽  
Grade 3

309 Background: The long-term efficacy and tolerability of nivolumab (NIVO) 3 mg/kg + ipilimumab (IPI) 1 mg/kg Q3W × 4 doses followed by NIVO 3 mg/kg Q2W for previously untreated advanced RCC (aRCC) demonstrated in the registrational CheckMate 214 clinical trial was based on patients (pts) with a predominantly clear cell component. CheckMate 920 (NCT02982954) is a US community-based, multi-arm, phase IIIb/IV clinical trial of NIVO+IPI treatment in pts with previously untreated aRCC and clinical features mostly excluded from phase III trials. Here, we present the safety and efficacy results for the cohort of pts with nccRCC from CheckMate 920, a patient population with a poor prognosis and without a definitive effective treatment. Methods: Pts with previously untreated advanced/metastatic nccRCC, Karnofsky performance status ≥ 70%, and any International Metastatic Renal Cell Database Consortium risk received NIVO 3 mg/kg + IPI 1 mg/kg (NIVO3+IPI1) Q3W × 4 doses followed by NIVO 480 mg Q4W for ≤ 2 years or until disease progression/unacceptable toxicity. The primary endpoint was incidence of any-causality grade ≥ 3 immune-mediated adverse events (imAEs) within 100 days of last dose of study drug. Key secondary endpoints: progression-free survival (PFS) and objective response rate (ORR) by RECIST v1.1 (both per investigator), duration of response (DOR), and time to response (TTR). Exploratory endpoints included overall survival (OS). Results: Of 52 treated pts with nccRCC, 69.2% were men; median age was 64 years (range, 23–86), and 28.8% had sarcomatoid features. Histological subtypes were papillary (34.6%), chromophobe (13.5%), translocation associated (3.8%), collecting duct (3.8%), renal medullary (1.9%), or unclassified (42.3%). With 24.1 months minimum follow-up, median duration of therapy (range) was 3.5 months (0.0–25.8) for NIVO and 2.1 months (0.0–3.9) for IPI. Median (range) number of doses received was 4.5 (1–28) for NIVO and 4.0 (1–4) for IPI. No grade 5 imAEs occurred. Grade 3–4 imAEs (n = 52) by category were diarrhea/colitis (7.7%), rash (5.8%), nephritis and renal dysfunction (3.8%), hepatitis (1.9%), adrenal insufficiency (1.9%), and hypophysitis (1.9%). ORR (n = 46) was 19.6% (95% CI, 9.4–33.9). Two pts achieved complete response (papillary, n = 1; unclassified pathology, n = 1), 7 achieved partial response (papillary, n = 4; unclassified pathology, n = 3), and 17 pts had stable disease. Median TTR was 2.8 months (range, 2.1–4.8). Median DOR was not reached (range, 0.03+–27.8+); 8 of 9 responders remain without reported progression. Median PFS (n = 52) was 3.7 months (95% CI, 2.7–4.6). Median OS (n = 52) was 21.2 months (95% CI, 16.6–not reached). Conclusions: In pts with previously untreated nccRCC, a population with high unmet medical need, treatment with NIVO3+IPI1 Q3W followed by NIVO 480 mg Q4W showed no new safety signals, and encouraging antitumor activity. Clinical trial information: NCT02982954 .

Safety and efficacy outcomes with nivolumab plus ipilimumab in patients with advanced renal cell carcinoma and low Karnofsky performance status: Results from the CheckMate 920 trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 315-315
Author(s):  
Thomas E. Hutson ◽  
Bradley Curtis Carthon ◽  
Jeffrey Yorio ◽  
Sunil Babu ◽  
Heidi Ann McKean ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Adverse Events ◽  
Clear Cell ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Objective Response ◽  
Safety And Efficacy ◽  
Grade 3

315 Background: Combination therapy with nivolumab + ipilimumab (NIVO+IPI) has demonstrated long-term efficacy and tolerability for patients (pts) with previously untreated advanced renal cell carcinoma (aRCC). Most pivotal clinical trials in pts with aRCC have excluded pts with low Karnofsky performance status (KPS; < 70%). CheckMate 920 is a multi-arm, phase IIIb/IV, open-label clinical trial of NIVO+IPI treatment in pts enrolled in a community practice setting with aRCC and a high unmet medical need. We present safety and efficacy results for the cohort of pts with aRCC of any histology and KPS 50%–60% from CheckMate 920 (NCT02982954). Methods: Pts with previously untreated advanced/metastatic RCC and KPS 50%–60% received NIVO 3 mg/kg + IPI 1 mg/kg Q3W × 4 doses followed by 480 mg NIVO Q4W for ≤ 2 years or until disease progression/unacceptable toxicity. The primary endpoint was incidence of grade ≥ 3 immune-mediated adverse events (imAEs) within 100 days of last dose of study drug. Key secondary endpoints included progression-free survival (PFS) and objective response rate (ORR) by RECIST v1.1 (both per investigator). Exploratory endpoints included overall survival (OS). Results: Of 25 treated pts with KPS 50%–60%, 76% were men; median age was 67 years (range, 34–81). IMDC risk was favorable in 0%, intermediate in 32%, and poor in 68% of pts; 84% had clear cell and 16% had non-clear cell RCC histology. With a minimum follow-up of 25 months, median duration of therapy (95% CI) was 2.3 months (2.1–7.7) for NIVO and 2.1 months (2.1–2.1) for IPI. The median number of doses (range) received was 4 (1–27) for NIVO and 4 (1–4) for IPI; 76% of pts received ≥ 4 NIVO doses and 68% received all 4 IPI doses. The only grade 3–4 imAEs by category were hepatitis (4.0%) and adrenal insufficiency (4.0%). No grade 5 imAEs occurred. Overall, 4 (16%) pts discontinued due to any-grade adverse events (n = 1 each for elevated AST, malignant neoplasm progression, back pain, and acetabulum fracture). Of 18 evaluable pts, ORR was 33.3% (95% CI, 13.3–59.0); no pts had a complete response and 6 had partial response. Median time to objective response was 4.5 months (range, 2.5–24.7). Median duration of objective response was 20.6 months (range, 0.03+–24.2+). Median PFS was 4.6 months (95% CI, 2.5–14.8). Median OS was 15.6 months (95% CI, 5.3–25.1). Conclusions: NIVO+IPI demonstrated an acceptable safety profile and promising antitumor activity in pts with previously untreated aRCC and KPS 50%–60%. The combination was tolerated at a dose intensity similar to that observed in clinical trials conducted in pts with higher KPS (≥ 70%). These data support the value of NIVO+IPI in pts who may not be considered ideal candidates for this therapy and consequently may have limited treatment options. Clinical trial information: NCT02982954 .

Safety and efficacy of nivolumab plus ipilimumab (NIVO+IPI) in patients with advanced renal cell carcinoma (aRCC) with brain metastases: Interim analysis of CheckMate 920.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4517-4517 ◽  
Author(s):  
Hamid Emamekhoo ◽  
Mark Olsen ◽  
Bradley Curtis Carthon ◽  
Alexandra Drakaki ◽  
Ivor John Percent ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Antitumor Activity ◽  
Brain Metastases ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Objective Response ◽  
Safety And Efficacy ◽  
Immune Mediated ◽  
Grade 3

4517 Background: Previous clinical trials of patients (pts) with aRCC, including CheckMate 214, have mostly excluded pts with brain metastases. However, antitumor activity in pts with brain metastases has been observed in pts with melanoma treated with NIVO 1 mg/kg + IPI 3mg/kg and pts with non-small cell lung cancer treated with NIVO 240 mg + IPI 1mg/kg. CheckMate 920 is an ongoing, phase 3b/4 clinical trial of NIVO + IPI treatment in pts with aRCC with a high unmet medical need. Here, we present the safety and efficacy interim results for the cohort of pts with brain metastases. Methods: Pts with previously untreated aRCC of any histology, with asymptomatic brain metastases (not on corticosteroids or receiving radiation), and Karnofsky performance status ≥70% were assigned to treatment with NIVO 3 mg/kg + IPI 1 mg/kg every 3 weeks for 4 doses, followed by NIVO 480 mg every 4 weeks. Pts were treated until disease progression, unacceptable toxicity, or for a maximum of 2 years. The primary endpoint was the incidence of high-grade immune-mediated adverse events (IMAEs). Key secondary endpoints included progression-free survival (PFS) and objective response rate (ORR) by RECIST v1.1 per investigator. Exploratory endpoints included additional safety analyses and overall survival (OS). Results: Overall, 28 patients were enrolled in the brain metastases cohort. With a minimum follow-up of 6.47 months, grade 3-4 IMAEs within 100 days of last dose were reported in 6 cases. The grade 3-4 IMAEs observed in ≥ 1 patient were diarrhea, colitis, diabetic ketoacidosis, immune-mediated hepatitis, hypophysitis, and rash of any type (n = 1 each). No treatment-related grade 5 IMAEs were reported. ORR by RECIST v1.1 per investigator in all treated subjects was 28.6% (95% CI 13.2–48.7). Median PFS in all treated subjects was 9.0 months (95% CI 2.9–not estimable [NE]). Median OS has not been reached (95% CI 13.1–NE). Conclusions: In pts with aRCC and brain metastases who are often excluded from clinical trials, NIVO + IPI treatment showed a safety profile consistent with previous reports of this dosing regimen, with encouraging antitumor activity. Clinical trial information: NCT02982954.

The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) expanded access trial: Safety and efficacy in patients (pts) with non-clear cell (NCC) renal cell carcinoma (RCC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5036-5036 ◽  
Author(s):  
W. M. Stadler ◽  
R. A. Figlin ◽  
M. S. Ernstoff ◽  
B. Curti ◽  
K. Pendergrass ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Severe Renal Impairment ◽  
Collecting Duct ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Open Label ◽  
Grade 3

5036 Background: A phase III trial showed that sorafenib (SOR) doubled progression-free survival (PFS) in previously treated pts with clear cell RCC. Activity of SOR in pts with NCC RCC has not been previously reported. Methods: Pts eligible for this open-label, nonrandomized trial in North America were not eligible for other SOR clinical trials, had recovered from prior treatment-related toxicity, and had advanced RCC; ECOG PS of 0–2; age =15 yrs; no treatment with other investigational drugs within 4 wks; life expectancy >2 mos; no active coronary artery disease, ischemia or hypertension; and no severe renal impairment requiring dialysis. In the US, ARCCS enrollment ended with SOR approval in 12/05, and pts were transitioned to commercial drug with NCC pts being eligible for an additional 6-mo follow-up in an extension protocol (EP), which was designed to better assess PFS in NCC. Tumor assessments and radiological evaluations were conducted every 4 wks in the main protocol and every 8 wks in the EP. Results: Of 2,488 pts valid for safety in ARCCS, 212 (8.5%) had NCC RCC classified as papillary, chromophobe, collecting duct, or oncocytoma, of whom 24 enrolled in the EP. Baseline characteristics and efficacy are shown in the table . Grade 3 and 4 adverse events (AEs) with > 2% incidence across all histologies included fatigue 7.1%, hand-foot skin reaction 6.6%, rash/ desquamation 6.2%, hypertension 4.7%, abdominal pain 3.8% dyspnea 3.8%, pleural effusion 3.3%, nausea 3.8%, vomiting 2.4%, and ascites 2.4%. Grade 3 and 4 serious AEs were reported in 20% of patients. Of those enrolled in the EP with NCC, median PFS was 34.5 wks (65.2% censored). Conclusions: SOR was well tolerated among pts with NCC RCC. Within the limitations of no central pathologic review, SOR toxicity in NCC RCC was similar to that in the broader ARCCS population and SOR may have antitumor activity in papillary and chromophobe subtypes. [Table: see text] [Table: see text]

scholarly journals Phase III Trial of Bevacizumab Plus Interferon Alfa Versus Interferon Alfa Monotherapy in Patients With Metastatic Renal Cell Carcinoma: Final Results of CALGB 90206

2010 ◽  
Vol 28 (13) ◽  
pp. 2137-2143 ◽  
Author(s):  
Brian I. Rini ◽  
Susan Halabi ◽  
Jonathan E. Rosenberg ◽  
Walter M. Stadler ◽  
Daniel A. Vaena ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Interferon Alfa ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Grade 3

Purpose Bevacizumab is an antibody that binds vascular endothelial growth factor and has activity in metastatic renal cell carcinoma (RCC). Interferon alfa (IFN-α) is the historic standard initial treatment for RCC. A prospective, randomized, phase III trial of bevacizumab plus IFN-α versus IFN-α monotherapy was conducted. Patients and Methods Patients with previously untreated, metastatic clear cell RCC were randomly assigned to receive either bevacizumab (10 mg/kg intravenously every 2 weeks) plus IFN-α (9 million units subcutaneously three times weekly) or the same dose and schedule of IFN-α monotherapy in a multicenter phase III trial. The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rate, and safety. Results Seven hundred thirty-two patients were enrolled. The median OS time was 18.3 months (95% CI, 16.5 to 22.5 months) for bevacizumab plus IFN-α and 17.4 months (95% CI, 14.4 to 20.0 months) for IFN-α monotherapy (unstratified log-rank P = .097). Adjusting on stratification factors, the hazard ratio was 0.86 (95% CI, 0.73 to 1.01; stratified log-rank P = .069) favoring bevacizumab plus IFN-α. There was significantly more grade 3 to 4 hypertension (HTN), anorexia, fatigue, and proteinuria for bevacizumab plus IFN-α. Patients who developed HTN on bevacizumab plus IFN-α had a significantly improved PFS and OS versus patients without HTN. Conclusion OS favored the bevacizumab plus IFN-α arm but did not meet the predefined criteria for significance. HTN may be a biomarker of outcome with bevacizumab plus IFN-α.

Phase III study of nab-paclitaxel (nab-P) plus gemcitabine (Gem) versus Gem alone in patients (pts) with metastatic pancreatic adenocarcinoma (mPC): Subgroup analysis of Canadian pts from the MPACT trial.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 439-439
Author(s):  
Mustapha Ali Tehfe ◽  
Scot D. Dowden ◽  
Hagen F. Kennecke ◽  
Robert Hassan El-Maraghi ◽  
Bernard Lesperance ◽  
...  
Keyword(s):  
Karnofsky Performance Status ◽  
Performance Status ◽  
Pancreatic Head ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Common Grade ◽  
Grade 3 ◽  
Intent To Treat

439 Background: Weekly nab-P + Gem is a new option for first-line treatment (Tx) of mPC. In the MPACT trial, nab-P/Gem demonstrated superior overall survival (OS; primary endpoint) vs Gem alone as first-line Tx of mPC (Table). Here we report a subgroup analyses evaluating the efficacy and safety outcomes with nab-P + Gem vs Gem alone from the Canadian cohort of the MPACT trial. Methods: Previously untreated pts (N = 861) with mPC were randomized 1:1 (stratified by Karnofsky Performance Status [KPS], region, and the presence of liver metastases) to receive nab-P 125 mg/m2 + Gem 1000 mg/m2 on days 1, 8, and 15 of each 28-day cycle or Gem 1000 mg/m2 weekly for 7 weeks followed by 1 week of rest (cycle 1) and then days 1, 8, and 15 of each 28-day cycle (cycle ≥ 2). Results: 63 pts from Canada enrolled in the MPACT trial. Baseline pt characteristics were well balanced. Median age was 61 years and KPS was similar for both groups and comparable to the intent-to-treat (ITT) populations. Primary lesion in the pancreatic head was more common among pts in the nab-P + Gem vs Gem arm (55% vs 30%); use of biliary stent was similar (33% nab-P + Gem; 27% Gem). Median OS and progression-free survival (PFS) were longer with nab-P + Gem vs Gem (Table). Median Tx duration was 4.2 mo with nab-P + Gem vs 3.2 mo with Gem. Use of subsequent therapy was 30% in the nab-P + Gem arm vs 43% in the Gem arm. The median relative dose intensity for Gem was similar in each arm (81% nab-P + Gem vs 85% Gem). The most common grade ≥ 3 AEs for nab-P + Gem vs Gem were neutropenia (22% vs 10%), fatigue (34% vs 33%), and neuropathy (25% vs 0%). Conclusions: Canadian pts participating in MPACT were similar to the ITT population and nab-P + Gem was well tolerated and showed improved median OS, PFS, and ORR vs Gem alone, although not statistically significant (likely due to the small number of pts). Clinical trial information: NCT00844649. [Table: see text]

A randomized phase II trial comparing different schedules of nab-paclitaxel (nabP) combined with gemcitabine (GEM) as first line treatment for metastatic pancreatic adenocarcinoma (mPDAC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4100-4100 ◽  
Author(s):  
Philippa Corrie ◽  
Wendi Qian ◽  
Bristi Basu ◽  
Juan W. Valle ◽  
Stephen Falk ◽  
...  
Keyword(s):  
Cytidine Deaminase ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Objective Response ◽  
Pancreatic Head ◽  
Progression Free Survival ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Age Range

4100 Background: NabP+GEM chemotherapy improves survival compared with GEM monotherapy as treatment for mPDAC. A PDAC mouse model suggested that nabP potentiates GEM activity by reducing cytidine deaminase levels and scheduling may be critical to optimise clinical benefit. Methods: Patients (pts) were randomised to receive standard concomitant (CON) nabP+GEM or sequential (SEQ) administration, with nabP given 24 hours before GEM. After 6 cycles, pts benefiting from treatment could continue the same regimen until disease progression. The primary endpoint was progression-free survival (PFS) by RECIST v1.1; secondary endpoints included safety, objective response rate (ORR), overall survival (OS) and quality of life (QoL). Serial blood and baseline tumour samples were collected for exploratory biomarkers. Results: Between March 2014 and 2016, 146 pts (71 SEQ, 75 CON) were recruited. Median age (range) was 66 (45-82) years; Karnofsky performance status was 70 (in 12% pts), 80 (27%), 90 (38%) or 100 (24%); 47% had pancreatic head primaries; 84% had liver metastases. Median no. cycles received was 4 SEQ, 3 CON; 51 pts (35%) received ≥6 cycles of treatment (42% SEQ, 28% CON). A 24+2hr interval was achieved in > 90% SEQ admin. Grade ≥3 adverse events experienced by ≥10% pts (SEQ, CON) were neutropaenia (54%, 30%; p = 0.003), febrile neutropaenia (12%, 12%), fatigue (22%, 15%), vomiting (7%, 11%) and anaemia (10%, 5%). G-CSF was administered at local investigator's discretion to 35 pts (23 SEQ, 12 CON; p = 0.015). To date, 112 pts have died. 6 month (m) PFS by SEQ and CON arms were 47% and 33%; median PFS were 5.8 and 4.0m; hazard ratio (HR) = 0.66, 95% CI = 0.46-0.95; 12m OS by SEQ and CON arms were 29% and 26%; median OS were 10.1 and 7.9m; HR = 0.88, 95% CI = 0.61-1.29. ORR was 50% SEQ and 33% CON (p = 0.065). Mean baseline QoL Global health status score was 60.6 SEQ and 63.4 CON. The mean change in QoL score from baseline at 24 weeks was -2.1 SEQ and -12.1 CON. Conclusions: Sequential delivery of nabP combined with GEM trended towards improving all clinically relevant efficacy end points: PFS, OS, and ORR. Translational correlates will be reported in due course. Clinical trial information: ISRCTN71070888.

Phase III Randomized Controlled Trial Comparing the Survival of Patients With Unresectable Hepatocellular Carcinoma Treated With Nolatrexed or Doxorubicin

2007 ◽  
Vol 25 (21) ◽  
pp. 3069-3075 ◽  
Author(s):  
Robert G. Gish ◽  
Camillo Porta ◽  
Lucian Lazar ◽  
Paul Ruff ◽  
Ronald Feld ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Karnofsky Performance Status ◽  
Controlled Trial ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Complete Response ◽  
Phase Iii ◽  
Study Objective

PurposeThe study objective was to compare the overall survival (OS) of patients with unresectable or metastatic hepatocellular carcinoma (HCC) treated with nolatrexed (NOL) or doxorubicin (DOX).Patients and MethodsPatients from North America, Europe, and South Africa (N = 445) with HCC were randomly assigned to receive NOL or DOX. Eligible patients had Karnofsky performance status (KPS) ≥ 60%, Cancer of the Liver Italian Program (CLIP) score ≤ 3, and adequate organ function. Primary end point was OS. Secondary end points included progression-free survival (PFS), objective response rates, and safety. The treatment groups were well-balanced with regards to age, sex, ethnic origin, and underlying liver disease. Randomization was stratified according to KPS and CLIP score.ResultsAt the time of the final analysis, 377 patients had died. Median OS was 22.3 weeks for NOL and 32.3 weeks for DOX (P = .0068). The hazard ratio was 0.753 in favor of DOX. Objective response rate (complete response [CR] plus partial response [PR]) was 1.4% for NOL and 4.0% for DOX. Median PFS was 12 weeks for NOL and 10 weeks for DOX (P = .7091). Median time to treatment failure was 8.4 weeks for NOL and 9.1 weeks for DOX (P = .0969). Grade 3 and 4 stomatitis, vomiting, diarrhea, and thrombocytopenia were more common in the NOL arm. Alopecia was more common in the DOX arm. More patients were withdrawn from study for toxicity in the NOL arm than in the DOX arm.ConclusionNOL showed minimal activity in this phase III trial. Further exploration at this dose and schedule in HCC is not warranted.

The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) expanded access trial: Safety and efficacy in patients (pts) with prior bevacizumab (BEV) treatment

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5041-5041 ◽  
Author(s):  
H. A. Drabkin ◽  
R. A. Figlin ◽  
W. M. Stadler ◽  
T. E. Hutson ◽  
J. Hajdenberg ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Severe Renal Impairment ◽  
Prior Treatment ◽  
Phase Iii ◽  
Safety And Efficacy ◽  
Expanded Access ◽  
Hemorrhagic Event ◽  
Grade 3

5041 Background: Sorafenib (SOR) is an oral multi-kinase inhibitor of tumor-cell angiogenesis and proliferation. Phase III (TARGETs) data have demonstrated prolonged progression-free survival in pts with advanced clear cell renal cell carcinoma (RCC) in whom prior therapy failed. Activity of SOR following treatment with BEV, an anti-vascular endothelial growth factor and antiangiogenic monoclonal antibody, has not been evaluated. Methods: A subset analysis was conducted to describe safety and efficacy in the SOR expanded access program in North America for pts receiving prior BEV. Inclusion criteria for this open-label, nonrandomized trial included advanced RCC; ineligibility for, or lack of access to, other SOR clinical trials; age =15 years; ECOG PS of 0–2; recovery from prior treatment; adequate prior treatment of brain metastases. Major exclusion criteria included life expectancy <2 months; active coronary artery disease, ischemia or hypertension; severe renal impairment requiring dialysis. Pts previously treated with BEV required =28 days from last dose, no =Grade 3 hemorrhagic episode during therapy, and no history of =Grade 2 hemorrhagic event 6 mos prior to BEV treatment. Results: Of the 2,488 pts in ARCCS valid for safety analysis, 289 pts had received prior BEV: 65% male with median age 61 yrs. Grade 3 and 4 toxicities occurring in >2% of prior BEV pts included hand-foot skin reaction 9.0%; fatigue 6.9%; hypertension 4.8%; dehydration, dyspnea, anorexia, and abdominal pain 3.1%; back pain, rash/desquamation, and mucositis 2.8%; pleural effusion and diarrhea 2.1%. Of the 195 BEV-pretreated pts evaluable for response, 152 (77.5%) had stable disease and 5 (2.5%) had confirmed partial responses (PR). There were 26 (13.3%) unconfirmed PRs reported according to RECIST, 4 of which missed a second scan due to US ARCCS enrollment ceasing upon FDA approval of SOR in 12/05. Conclusions: We observed activity of SOR following BEV therapy for advanced RCC. AEs in this subset were generally well tolerated and similar to those in the overall ARCCS population. Further investigation is warranted to elucidate mechanisms for response to SOR following prior antiangiogenic treatment. [Table: see text]

Clinical outcomes by nephrectomy status in METEOR, a randomized phase 3 trial of cabozantinib (cabo) vs everolimus (eve) in patients (pts) with advanced renal cell carcinoma (RCC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4570-4570
Author(s):  
Nizar M. Tannir ◽  
Thomas Powles ◽  
Bernard J. Escudier ◽  
Frede Donskov ◽  
Viktor Grünwald ◽  
...  
Keyword(s):  
Risk Group ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Objective Response ◽  
Palliative Therapy ◽  
Progression Free Survival ◽  
Tumor Grade ◽  
Phase 3 ◽  
Grade 3 ◽  
To Receive

4570 Background: Most pts with advanced RCC undergo nephrectomy (Nx) as curative or palliative therapy. In a retrospective analysis of pts treated with targeted therapy, pts who were older and had more comorbidities and higher tumor grade were less likely to have had Nx. Pts without Nx had shorter overall survival (OS) than pts with Nx (Hanna, J Clin Oncol 2016). Here we report outcomes for cabo vs eve in pts with advanced RCC with or without prior Nx in the phase 3 METEOR trial (NCT01865747). Methods: 658 pts with clear cell RCC and ≥1 prior VEGFR TKI were randomized 1:1 to receive cabo at 60 mg qd or eve at 10 mg qd. Stratification was by MSKCC risk group and number of prior VEGFR TKIs. Endpoints included progression-free survival (PFS), OS, and objective response rate (ORR). Results: 85% of enrolled pts had prior Nx of which 7% were partial; 15% had no prior nephrectomy (NoNx). Baseline characteristics, including Karnofsky performance status (KPS), MSKCC risk group, time from diagnosis to randomization, and median sum of diameters (SoD) for tumor target lesions, were less favorable for the NoNx subgroup (Table). Improved PFS and OS with cabo vs eve were observed regardless of Nx status. For the Nx subgroup, the hazard ratio (HR) was 0.51 (95% CI 0.41-0.64) for PFS and 0.66 (95% CI 0.52-0.84) for OS; for the NoNx subgroup, the HR was 0.51 (95% CI 0.30-0.86) for PFS and 0.75 (95% CI 0.44-1.27) for OS. Median OS was longer in the Nx subgroup for both treatment arms (Table). ORR per independent radiology committee (IRC) for cabo vs eve was 17% vs 4% for Nx and 21% vs 2% for NoNx. Grade 3 or 4 adverse events for both subgroups were generally consistent with the safety profiles of cabo and eve in the overall population. Conclusions: Cabo improved PFS, ORR, and OS compared with eve in pts with advanced RCC irrespective of nephrectomy status. Clinical trial information: NCT01865747. [Table: see text]

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