A randomized phase II trial of pazopanib (PAZ) versus temsirolimus (TEM) in patients (pts) with advanced clear-cell renal cell carcinoma (aCCRCC) of intermediate and poor-risk (the TemPa trial).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 583-583 ◽  
Author(s):  
Nizar M. Tannir ◽  
Jeremy Aaron Ross ◽  
Catherine E Devine ◽  
Anuradha Chandramohan ◽  
Xuemei Wang ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Intermediate Risk ◽  
Cell Renal Cell Carcinoma ◽  
Exact Test ◽  
Poor Risk ◽  
Kaplan Meier ◽  
Alternative Agent ◽  
Treatment Naïve ◽  
To Receive

583 Background: TEM has level 1 evidence in aRCC with poor-risk disease. No trial compared a VEGFR-TKI with TEM as first-line (1L) therapy in this disease state. Methods: We randomly assigned (1:1) treatment-naïve pts with aCCRCC and > = 3 risk factors (as per Hudes et al., NEJM 2007) to receive PAZ 800 mg po qd or TEM 25 mg iv qw. Pts were offered to receive the alternative agent at disease progression (PD). The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR) and safety. A blinded radiologist assessed the radiographic response using RECIST v1.1. A sample size of 90 pts was based on an assumption of improved median PFS from 3.8 mo with TEM to 6.1 mo with PAZ. Pts were stratified by prior nephrectomy (Nx). The Kaplan-Meier method was used for PFS and OS analysis, and the Fisher’s exact test was used for comparison of ORR between PAZ and TEM. Results: The study was closed to new patient enrollment when the results of the CheckMate 214 and CABOSUN studies were presented at ESMO 2017. A total of 69 pts were eligible and evaluable (median age 61, 52 males [75%], 44 [64%] had poor-risk by IMDC criteria). Thirty pts [43%] had prior Nx. Thirty-five pts received PAZ (intermediate-risk 13, poor-risk 22) and 34 pts received TEM (intermediate-risk 12, poor-risk 22). Of the 69 pts, 67 had PD or died. The median PFS was 5.2 mo (95% CI: 3.6 –7.4) for PAZ and 2.6 mo (95% CI: 1.9 –4.2) for TEM (p = 0.16). In 1 pt, no date of death was available. Of the remaining 68 pts, 58 (85.3%) have died. The median OS was 12.0 mo (95% CI: 8.3–20.1) for PAZ and 7.4 mo (95% CI: 5.3–17.4) for TEM (p = 0.61). Sixty-eight pts were evaluable for response: 9/35 pts (26%) who received PAZ and 2/33 pts (6%) who received TEM had partial response (p = 0.046). Adverse events (AEs) were consistent with the known safety profiles of PAZ and TEM. Only 2 pts in each arm discontinued treatment due to AEs. Conclusions: PAZ extended PFS and OS and yielded a significantly higher ORR than TEM as 1L therapy in pts with aCCRCC and intermediate/poor-risk disease. Clinical trial information: NCT01392183.

Sunitinib in patients with pancreatic neuroendocrine tumors (panNETs): Exploratory pharmacogenomic analyses.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 255-255
Author(s):  
Nicola Fazio ◽  
Jean-Francois Martini ◽  
Adina-Emilia Croitoru ◽  
Michael Schenker ◽  
Sherry Li ◽  
...  
Keyword(s):  
Protein Transport ◽  
Proportional Hazards ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Nucleotide Polymorphisms ◽  
Exact Test ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Treatment Naïve

255 Background: In a phase IV trial (NCT01525550), median progression-free survival (PFS) was 13.2 mo in sunitinib-treated patients (pts) with well-differentiated panNETs. Objective response rate (ORR) was 24.5% and median overall survival (OS) was 37.8 mo. Exploratory analyses evaluated potential associations between single nucleotide polymorphisms (SNP) in genes involved in angiogenesis, protein transport or inflammatory response and clinical outcomes. Methods: Blood samples were genotyped using TaqMan assays for 12 SNPs previously associated with panNET risk, prognosis or drug effect. Associations between SNP and PFS or OS were assessed by comparing genotypes within treatment-naïve (TN), previously treated (PT) and combined groups, and within a genotype between treatment groups, using Kaplan-Meier analysis and Cox proportional hazards models. Fisher’s exact test was used for association between ORR and genotype. PFS and ORR were investigator-assessed. P values displayed are unadjusted and Bonferroni method was used for multiplicity adjustment. Results: 56 pts were genotyped: 25 TN and 31 PT. There were no significant associations between genotype and PFS or OS but there was a trend toward shorter PFS in pts with VEGFR1 rs9554320 C/A versus C/C (hazard ratio [HR] 1.78; 95% confidence interval [CI] 0.83–3.82; p = 0.117) and VEGFR1 rs9582036 A/C versus A/A (HR 1.88; 95% CI 0.9–3.93; p = 0.102). The genotypes G/G of VEGFA rs2010963 (p = 0.041) , G/G of VEGFA rs833068 (p = 0.041) and A/C of VEGFR1 rs9582036 (p = 0.046) showed a trend toward a higher ORR in the PT versus TN group. Genotype T/T of VEGFR2 rs7692791 (p = 0.103) showed a trend toward to a lower ORR in the TN versus PT group. Higher ORR was associated with IL1B rs16944 G/A versus G/G (46.4% vs 4.5%; p = 0.001) in the combined group. Conclusions: Potential associations between ORR and VEGFA rs2010963 and rs833068, VEGFR1 rs9582036 and VEGFR2 rs7692791 were observed. IL1B rs16944 was significantly associated with ORR, consistent with the role of IL1B in panNET etiology and development. Most correlations were not significant after adjustment for multiplicity. Clinical trial information: NCT01525550.

Correlation of chromosome (Chr) 14 loss and 5q gain with outcomes of pazopanib treatment in patients (pts) with metastatic clear cell renal cell carcinoma (mRCC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4605-4605 ◽  
Author(s):  
Gary R. Hudes ◽  
Jianming Pei ◽  
Yuan Liu ◽  
Robert C. Gagnon ◽  
Christopher Carpenter ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Cell Renal Cell Carcinoma ◽  
Treatment Benefit ◽  
Kaplan Meier ◽  
Specific Tumor ◽  
Important Challenge ◽  
Independent Review ◽  
Dna Copy Number Alterations ◽  
Tumor Dna

4605 Background: The identification of molecular prognostic and/or predictive determinants of outcome in pts with mRCC is an important challenge. We hypothesized that specific tumor DNA copy number alterations (CNAs) - loss of chr 14 or 14q (14/14q-), and gain of chr 5q (5q+) may predict likelihood of pazopanib treatment benefit in pts with mRCC. Methods: Pts DNA samples from the Phase II (VEG102616) pazopanib trial were analyzed by using Affymetrix OncoScan. Copy no. data were moving smoothed and normalized. The copy no. and allele difference were profiled according to their chromosome locations to interrogate CNA and LOH. Objective response (OR, RECIST) and progression free survival (PFS) were determined by investigators (IN) and an independent review (IR) committee. OR and PFS data were analyzed using exact and Kaplan-Meier tests. Results: Tumor DNA samples from 75 pts were adequate for CNA analysis. 14/14q- was found in 35/75 pts (46.7%), and 5q+ was found in 37/75 (49.3%). 14/14q- was present in the tumors of 12/31 pts (39%) with OR by IR compared with 23/44 (52%) nonresponding pts (p=0.347). 14/14q- did not affect PFS. 5q+ was present in tumors of 17/31 pts (55%) with OR and 20/44 (45%) nonresponding pts (p=0.486). PFS was longer in pts with 5q+ tumors compared with those without 5q+ (log rank p=0.026), with median PFS of 66 vs 35 wks, respectively. The odds of achieving OR decreased as the total number of chromosomal gains/losses increased (p=0.032, odds ratio 0.49), but this had no effect on PFS. In exploratory analysis, we examined the combined effect of both 14/14q- and 5q+ on PFS (Table). Conclusions: Pts with 5q+ tumors have significantly longer PFS, with no effect on OR rate. While 14/14q- alone had no effect on outcomes, the combination of 5q+ and no 14/14q- was associated with significantly greater PFS. Pts with more genetically complex tumors were less likely to obtain OR with pazopanib. [Table: see text]

Hypertension and myelosuppression as biomarkers of sunitinib efficacy in Chinese patients (pts) with metastatic renal cell carcinoma (mRCC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 426-426 ◽  
Author(s):  
Shukui Qin ◽  
Jie Jin ◽  
Jun Guo ◽  
Jin-Wan Wang ◽  
Fang-Jian Zhou ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Statistical Significance ◽  
Objective Response ◽  
Progression Free Survival ◽  
Chinese Patients ◽  
Rank Test ◽  
Open Label ◽  
Exact Test ◽  
Kaplan Meier ◽  
Open Label Phase

426 Background: In an open-label, phase IV study of sunitinib as 1st-line treatment (Tx) in Chinese pts with mRCC, median progression-free survival (PFS) and overall survival (OS) were 61.7 and 133.4 wk, respectively; objective response rate (ORR) was 31.1% (Ann Oncol 2012;23:851P). We retrospectively investigated correlations between on-Tx hypertension (HTN), neutropenia (N), and thrombocytopenia (T) and efficacy endpoints in pts from this trial. Methods: HTN was defined by either maximum systolic blood pressure ≥140 mm Hg (S-HTN) or maximum diastolic blood pressure ≥90 mm Hg (D-HTN). Using CTCAE assessment, N grade ≥2 and T grade >1 were used as cut-points for the analyses. Median PFS and OS were estimated by Kaplan−Meier method. The log-rank test was used to compare PFS and OS between groups with and without HTN, N grade ≥2, or T grade >1. Fisher’s exact test was used for ORR. Results: 102 pts were included in the HTN analyses, 60% with S-HTN versus 40% without S-HTN. Pts with S-HTN had greater ORR and longer PFS and OS than pts without S-HTN (Table). (Results were similar with D-HTN; see Table.) 103 pts were included in the N and T analyses, 67% with N grade ≥2 versus 33% with N grade <2, and 56% with T grade >1 versus 44% with T grade ≤1. Pts with N grade ≥2 had significantly greater ORR and significantly longer PFS and OS than pts with N grade <2 (Table). Pts with T grade >1 had greater ORR and significantly longer PFS and OS than pts with T grade ≤1 (Table). Conclusions: The developments of N grade ≥2 and T grade >1 during Tx with sunitinib were significantly associated with better outcome. Median PFS was more than twice as long for pts with S-HTN as for those without S-HTN, but the association did not reach statistical significance. [Table: see text]

Activity of third line (3L) therapy in patients with metastatic non-clear-cell renal cell carcinoma (mnccRCC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 650-650
Author(s):  
Annalisa Guida ◽  
Gwénaël Le Teuff ◽  
Emeline Colomba ◽  
Carolina Alveosta Silva ◽  
Flore Salviat ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Cell Renal Cell Carcinoma ◽  
Poor Risk ◽  
Retrospective Data Analysis ◽  
Kaplan Meier ◽  
The Impact

650 Background: Medical treatment of patients (pts) with mnccRCC remains uncertain, with no established standard treatment. In addition, no data on late line of treatment have been reported. The aim of this study was to investigate clinical outcome for patients receiving 3L therapy in mnccRCC Methods: Retrospective data analysis was performed using the IGRECC (Institut Gustave Roussy REnal Cell Carcinoma) database to describe clinical features and outcomes of 3L therapy in mnccRCC pts. Kaplan Meier estimation was applied for progression-free survival (PFS) and overall survival (OS) Results: Out of all pts with mRCC treated with a targeted therapy from 2005 to 2016, 202/1027 (20%) had mnccRCC. 117 (58%) received 2L therapy and 62 (30%) received 3L therapy. These pts had papillary RCC (61%), unclassified RCC (19), Xp11translocation renal cell carcinoma (13%) and chromophobe tumors (7%). The most common 3L therapies were: everolimus (29%), sorafenib (18%), other drugs in clinical trials (16%), sunitinib (11%), axitinib (10%) and cabozantinib (10%). Baseline characteristics are displayed in Table 1. With a median follow-up of 47 months (mo) (min: 0.7 max: 74), the median PFS is 5 mo (95%CI 2.7 - 5.8) and the median OS is 11.7 mo (95%CI 10 - 20). Pts with a favourable, intermediate and poor risk International Metastatic Renal Cell Cancer Database Consortium (IMDC) score had a median OS of 21 mo (95%CI 8 – NR), 11.9 mo (95%CI 10 – 25), and 6.2 mo (95%CI 2 – 8), respectively (p < 0.0001). One patient (2%) obtained a partial response and 26 pts (51%) achieved a stable disease, among 51 evaluable pts Conclusions: This is the first report investigating the impact of 3L systemic therapy in a rare population. Selected pts could benefit of more lines of therapy and IMDC score appears to stratify well prognostic groups, especially poor risk patients. [Table: see text]

Effect of comorbidities/comedications on treatment outcomes with sunitinib in patients (pts) with metastatic renal cell carcinoma (mRCC): Subgroup analyses from the STAR-TOR registry.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 631-631
Author(s):  
Stephan Bernhardt ◽  
Marcus Hubbe ◽  
Michael Rink ◽  
Lothar Bergmann ◽  
Martin Boegemann ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Real World ◽  
Objective Response ◽  
Progression Free Survival ◽  
Rank Test ◽  
Free Survival ◽  
Exact Test ◽  
Sunitinib Treatment ◽  
Kaplan Meier ◽  
Cutoff Date

631 Background: Sunitinib remains an important treatment option for mRCC, but the effect of comorbidities/comedications on sunitinib treatment outcomes have not been fully explored. Methods: Data were collated from STAR-TOR, an ongoing real-world registry. Cutoff date for analysis was 19 June 2019. This subgroup analysis assessed the presence or absence of hypertension (HTN), and the use or non-use of statins and proton pump inhibitors (PPIs), determined at the time of entry to the registry. Treatment endpoints were overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). OS and PFS were analyzed by Kaplan-Meier methods. Differences within subgroups were tested using Log-rank test for OS and PFS, and Fisher’s exact test for ORR. Results: 557 sunitinib-treated pts were analyzed; 366 had HTN and 191 did not, 130 used statins and 427 did not, and 165 used PPIs and 392 did not. Median (m) OS (95% confidence intervals) was similar in pts with and without HTN (25.4 [21.1, 31.5] vs 21.5 [15.2, 28.0] months; p = 0.215). mPFS (8.0 [6.5, 9.9] vs 6.3 [5.4, 8.2] months; p = 0.140) and ORR (31.2% vs 30.9%; p = 1.000) were also similar in pts with and without HTN. mOS was similar in pts who used statins vs those who did not (27.8 [20.2, 35.4] vs 24.0 [19.4, 27.3] months; p = 0.884), while mPFS was significantly longer in pts who used statins (9.4 [6.5, 13.6] vs 6.9 [5.7, 8.2] months; p = 0.044). ORR was 37.8% vs 29.0% in pts who did and did not use statins (p = 0.072). mOS was significantly shorter in pts who used PPIs vs those who did not (20.2 [14.9, 28.3] vs 25.7 [22.7, 33.0] months; p = 0.021). mPFS (5.8 [4.6, 8.2] vs 8.0 [6.5, 9.8] months; p = 0.091) and ORR (26.6% vs 33.0%; p = 0.177) were similar in pts who did and did not use PPIs. Conclusions: In sunitinib-treated pts with mRCC in a real-world registry, mPFS was significantly longer and there was a trend toward better ORR in pts who used statins, whereas mOS was significantly shorter and there was a trend toward shorter mPFS in pts who used PPIs. Common comedications may affect sunitinib treatment outcomes in pts with mRCC.

Efficacy of avelumab + axitinib (A + Ax) versus sunitinib (S) by IMDC risk group in advanced renal cell carcinoma (aRCC): Extended follow-up results from JAVELIN Renal 101.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4574-4574
Author(s):  
John B. A. G. Haanen ◽  
James Larkin ◽  
Toni K. Choueiri ◽  
Laurence Albiges ◽  
Brian I. Rini ◽  
...  
Keyword(s):  
Risk Group ◽  
Objective Response ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Complete Response ◽  
Duration Of Response ◽  
Treatment Naïve ◽  
Group A ◽  
To Receive

4574 Background: In the phase 3 JAVELIN Renal 101 trial (NCT02684006), treatment-naive patients with aRCC receiving A + Ax showed improved progression-free survival (PFS) and objective response rate (ORR) across International Metastatic RCC Database Consortium (IMDC) risk groups (favorable [F], intermediate [I], and poor [P]) compared with patients receiving S. Here we report updated efficacy results for A + Ax vs S by IMDC risk groups from the third interim analysis. Methods: Patients were randomized 1:1 to receive either A (10 mg/kg intravenously every 2 weeks) plus Ax (5 mg orally twice daily) or S (50 mg orally once daily) for 4 weeks (6-week cycle). Patients were categorized per IMDC risk group into F, I, and P subgroups, and outcomes were assessed for F, I, P, and I + P. Overall survival (OS) and PFS, ORR, complete response (CR), and duration of response (DoR) per investigator assessment (RECIST v1.1) were assessed. Results: The study enrolled 886 patients with aRCC. At data cutoff (Apr 2020), median (95% CI) follow-up for OS in the A + Ax was NR (42.2-NE) vs 37.8 (31.4-NE) months with S. The Table shows OS, PFS, ORR, CR, and DOR by IMDC risk group. A + Ax generally showed improved efficacy compared with S across IMDC groups. Conclusions: Consistent with previously reported results from prior interim analyses, extended follow-up confirms the efficacy benefits of A + Ax vs S across IMDC risk groups in patients with aRCC. Patients continue to be followed up for the final OS analysis. Clinical trial information: NCT02684006. [Table: see text]

Outcomes of patients (pts) with metastatic clear-cell renal cell carcinoma (mCCRCC) treated with second-line (2L) vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) after first-line (1L) immune checkpoint inhibitors (ICI).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 682-682 ◽  
Author(s):  
Amishi Yogesh Shah ◽  
Emily Lemke ◽  
Jianjun Gao ◽  
Anuradha Chandramohan ◽  
Matthew T. Campbell ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Cell Renal Cell Carcinoma ◽  
Impaired Wound Healing ◽  
Kaplan Meier ◽  
Best Response

682 Background: Little data exists on objective response rates (ORR), progression-free survival (PFS), and safety of 2L VEGFR-TKI after 1L ICI therapy in pts with mCCRCC. Methods: This is a retrospective study of pts with mCCRCC who received 2L VEGFR-TKI after progressive disease (PD) with 1L ICI. Tumor response was assessed by a blinded radiologist using RECIST 1.1. Descriptive statistics, the Fisher’s test, and Kaplan-Meier method were used. Results: We report on 43 pts who were treated at MDACC from 2015 till present. Median age at mCCRCC diagnosis was 59 years (range: 43-72). 33 pts had lung mets, 20 had LN mets, 14 had bone mets, and 3 had liver mets. As 1L therapy, 20 pts received nivolumab + ipilimumab, 14 received nivolumab + bevacizumab, and 9 received nivolumab. Median time on ICI therapy was 29.4 weeks. All pts had resolution of Grade 3/4 AEs from ICI and PD before initiation of VEGFR-TKI. One patient (2%) had CR, 17 pts (40%) had PR, and 25 pts (58%) had SD, leading to 100% disease control rate (DCR) as best response to 2L VEGFR-TKI. Median PFS was 10.0 months (95% CI: 7.4, NA). Estimated 1-yr overall survival (OS) was 87.5% (95% CI: 74.6 - 100). Seven pts (16%) discontinued VEGFR-TKI therapy because of AEs: Gr 3 transaminitis (3 on pazopanib), Gr 3 hand-foot skin reaction (1 on axitinib), impaired wound healing (1 on axitinib), and Gr 3 pancreatitis (1 on pazopanib, 1 on axitinib). Conclusions: In this retrospective study, we observed a 42% ORR, a 10-month median PFS, and a 100% DCR in pts with mCCRCC who received VEGFR-TKI after PD with ICI. These results inform the design of trials with 2L VEGFR-TKI after failure of ICI therapy. [Table: see text]

Cabozantinib versus sunitinib for previously untreated patients with advanced renal cell carcinoma (RCC) of intermediate or poor risk: Subgroup analysis of progression-free survival (PFS) and objective response rate (ORR) in the Alliance A031203 CABOSUN trial.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 582-582 ◽  
Author(s):  
Daniel J. George ◽  
Colin Hessel ◽  
Susan Halabi ◽  
Ben L. Sanford ◽  
M. Dror Michaelson ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Bone Metastases ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Poor Risk ◽  
Tumor Expression ◽  
Post Hoc ◽  
To Receive

582 Background: The randomized phase 2 CABOSUN trial (NCT01835158) compared cabozantinib (C) with sunitinib (S) as initial systemic therapy in patients (pts) with RCC of intermediate or poor risk. Compared with S, C improved both PFS and ORR as assessed by independent radiology review committee (IRC). Median PFS per IRC was 8.6 mo for C vs 5.3 mo for S (HR 0.48, 95% CI 0.31-0.74 two-sided p = 0.0008), and ORR per IRC was 20% vs 9%. Methods: 157 patients were randomized 1:1 to receive C (60 mg qd) or S (50 mg qd, 4 weeks on/2 weeks off) stratified by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group and the presence of bone metastases. Subgroup analyses of PFS per IRC and ORR per IRC are presented based on stratification factors, age, sex, baseline ECOG status, and MET tumor expression by immunohistochemistry. The primary endpoint was investigator-assessed PFS. PFS and ORR were evaluated by IRC in a post-hoc analysis. Results: 45% of pts were ≥65 years, 78% were male, 54% were ECOG 1 or 2, 19% were poor risk, and 36% had bone metastases. MET status was determined in 131 pts; of these 47% were MET positive. The HR for PFS per IRC favored C over S across all subgroups analyzed (Table). Subgroups with poor prognostic characteristics (poor risk, ECOG 1 or 2, presence of bone metastases) had shorter median PFS for both C and S. Odds ratios for ORR also favored C over S, with the highest C ORR in the MET positive subgroup (34% C vs 10% S). Conclusions: C was associated with improved PFS and ORR compared with S in previously untreated pts with advanced RCC irrespective of baseline characteristics. Clinical trial information: NCT01835158. [Table: see text]

A phase I/II trial of pazopanib alternating with bevacizumab in treatment-naïve metastatic clear cell renal cell carcinoma (CCRCC) patients: Phase I results.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 561-561
Author(s):  
Saby George ◽  
Laurie Herbst ◽  
Marcus Sikorski ◽  
Ann Marie Diraddo ◽  
Gissou Azabdaftari ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Trial ◽  
Kinase Inhibitors ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cell Renal Cell Carcinoma ◽  
Study Results ◽  
Treatment Naïve ◽  
Dose Levels

561 Background: Pazopanib as single agent and bevacizumab plus interferon were approved for use in metastatic RCC (MRCC) based on their ability to modulate the vasculature and prolong progression free survival. VEGF levels rose unopposed while using VEGF tyrosine kinase inhibitors (TKI) without break. We hypothesized that adding a break as well as bevacizumab which removes VEGF could prolong PFS in MRCC pts. Methods: This phase I trial was conducted in VEGF treatment naïve MRCC pts. This trial utilized a unique regimen of alternating Pazopanib (day 1-28) with bevacizumab (on days 36 and 50) in a 10-week cycle. The study employed a classic 3+3 design for dose escalation (dose levels in table 1). Safety utilized CTCAE version 4.0 and response evaluation was done using RECIST 1.1 criteria. The primary endpoint of this phase I trial was to find the recommended phase 2 dose (RP2D) of this novel regimen. Key secondary endpoints included objective response rate (ORR), safety/ toxicity and pharmacokinetics. Phase I safety committee acknowledged the completion and approved reporting of Phase I portion of this study. Results: This phase I study was conducted at two academic centers. Twenty-five pts were enrolled in the phase I portion. Median age was 64 years and 68% were male patients. The Commonest adverse events (AE) included fatigue (64%), diarrhea (52%), hypertension (48%), nausea (36%), dysgeusia (36%), vomiting (24%) and proteinuria (28%). The commonest grade 3/4 AE of more than 5% frequency included hypertension (20%) and proteinuria (12%). The dose levels 1 and 4 were expanded due to one DLT each and RP2D was established at dose level 4. The ORR was 25% among evaluable pts who completed at least one cycle of therapy (n=20). The median PFS of the ITT cohort (n=25) was 20.9 months. Conclusions: These data demonstrate that this novel regimen could be safely tested in a phase II trial. The safety and efficacy data suggest that this novel regimen could be optimal for MRCC patients with favorable/intermediate risk. Clinical trial information: NCT01684397. [Table: see text]

Immune-checkpoints inhibitors in metastatic non small cell lung cancer with rare histology.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9106-9106 ◽  
Author(s):  
Diego Signorelli ◽  
Roberto Ferrara ◽  
Claudia Proto ◽  
Giuseppe Lo Russo ◽  
Martina Imbimbo ◽  
...  
Keyword(s):  
Objective Response ◽  
Squamous Carcinoma ◽  
Progression Free Survival ◽  
Large Cell ◽  
Immune Checkpoints ◽  
Survival Analyses ◽  
Exact Test ◽  
Kaplan Meier ◽  
Line Of Therapy ◽  
Ecog Ps

9106 Background: Immune-checkpoints inhibitors (ICIs) have clearly improved prognosis of metastatic lung squamous carcinoma and adenocarcinoma, while their benefit remains uncertain in patients (pts) with rare NSCLC histotypes (RH). The study aim was to evaluate ICIs efficacy in RH. Methods: We retrospectively collected data from consecutive metastatic NSCLC pts treated with ICIs at our Institution from 4/2013 to 12/2018. Objective response rate (ORR) and disease control rate (DCR) were assessed. Fisher’s exact test was used to compare ORR and DCR in RH versus not-RH (NRH). Univariate and multivariate survival analyses were estimated by Kaplan-Meier and Cox progression hazard models. Results: Of 268 pts, 31 (11.6%) had RH: 16 sarcomatoid, 7 pulmonary enteric adenocarcinoma, 4 large cell neuroendocrine carcinoma and 4 adenosquamous carcinoma. In RH group, median age was 67 years old (range 41-81), most were males (71%) and smokers (90.3%); ECOG PS was: 0 (16.1%), 1 (67.8%) and 2 (16.1%). PD-L1 < 1%, 1-49%, ≥50% and unknown expression were reported in 22.6%, 19.3%, 35.5% and 22.6% pts, respectively. Twelve pts received ICIs as first and 19 as second or further-line. ORR was 22.6% in RH, 20.3% in NRH (p = 0.81); DCR was 35.5% in RH, 53.1% in NRH (p = 0.08). After a median follow-up of 20 months (m) (95% CI 4.0 – 36.7 m), median progression-free survival (PFS) was 2.6 m (95% CI 1.9-3.3 m) in RH vs 2.6 m in NRH (95% CI 2.1 – 3.0 m); median overall survival (OS) was 4.6 m (95% CI 0.03-12.0 m) in RH vs 9.2 m (95% CI 7.4 – 10.9 m) in NRH. No statistically significant differences were seen between the two groups (p = 0.729 for PFS, p = 0.601 for OS). At multivariate analyses adjusted for age, sex, smoke, PS, PD-L1 status, line of therapy and histotype (RH vs NRH), only low PS and first line treatment showed better PFS and OS (p < 0.001 and p = 0.003, respectively) in overall population. Conclusions: Our analysis, limited by the small and heterogeneous RH sample size, reported no significant differences between RH and NRH in terms of ORR, DCR and survival. However, looking at OS and DCR data, RH seem to have worse outcome. Correlation between histotype and pts characteristics and survival analyses in a larger cohort of ICIs treated NSCLC pts is ongoing. Specific prospective trials are needed to evaluate ICIs role in RH.

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