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]

Hand-foot syndrome (HFS) and asthenia/fatigue (A/F) as biomarkers of sunitinib efficacy in Chinese patients (pts) with metastatic renal cell carcinoma (mRCC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15622-e15622
Author(s):  
Shukui Qin ◽  
Jie Jin ◽  
Jun Guo ◽  
Jin-Wan Wang ◽  
Fang-Jian Zhou ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Objective Response ◽  
Early Time ◽  
Progression Free Survival ◽  
Time Dependent ◽  
Chinese Patients ◽  
Rank Test ◽  
Open Label ◽  
Exact Test ◽  
Landmark Analyses

e15622 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 HFS or A/F and efficacy endpoints in pts from this trial. Methods: AEs were recorded and graded using NCI CTCAE v3. 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 HFS or A/F. Fisher’s exact test was used for ORR. Multivariate and time-dependent covariate analyses were conducted to assess the influence of various prognostic factors on the association between AEs and efficacy and to address potential bias from longer drug exposure, respectively. Landmark analyses were used to compare outcomes in pts with and without HFS or A/F after 6 and 12 wk of Tx. Results: Of 103 pts included in the analyses, 67 (65%) and 54 (52%) had on-Tx HFS and A/F, respectively. Pts with HFS had greater ORR and significantly longer PFS and OS than pts without HFS (Table). Pts with A/F had greater ORR and longer PFS and OS than pts without A/F. By multivariate analysis, HFS was a significant predictor for both PFS and OS, and A/F was a significant predictor for PFS (Table). However, no findings were significant in the time-dependent covariate (Table) or landmark analyses (not shown). Conclusions: The development of HFS or A/F at any time during Tx with sunitinib was significantly associated with better outcome; however, time-dependent covariate and landmark analyses suggest that these AEs may not be reliable predictors of efficacy at early time points. Clinical trial information: NCT00706706. [Table: see text]

Association of immune related adverse events with superior outcomes in patients with hepatocellular carcinoma (HCC) treated with nivolumab.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16630-e16630
Author(s):  
Lorena Ostios-Garcia ◽  
David Ramiro-Cortijo ◽  
Mary Linton Bounetheau Peters ◽  
Andrea J. Bullock
Keyword(s):  
Adverse Events ◽  
Cox Regression ◽  
Statistical Significance ◽  
Onset Time ◽  
Progression Free Survival ◽  
Categorical Variables ◽  
Rank Test ◽  
Cancer Outcomes ◽  
Exact Test ◽  
Kaplan Meier

e16630 Background: Nivolumab, an anti-PD1 antibody, is FDA approved in patients (pts) with HCC. Anti-PD-1 promotes hyperstimulation of host immunity and is associated with a spectrum of toxicities known as immune-related adverse events (irAEs). In other malignancies, higher rates of irAEs are associated with improved cancer outcomes. This study shows correlation between irAEs and efficacy in pts with HCC treated with nivolumab. Methods: Demographic and toxicity data were collected retrospectively on all pts with HCC treated with nivolumab at a single institution from Jan 2012 – Sept 2019. Response was evaluated using RECISTv1.1. Adverse events were assessed according to CTCAEv5.0. Categorical variables were assessed by Fisher's exact test. Survival was estimated with the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses were performed by the Cox-regression model. Results: 30 pts were treated; irAEs were detected in 16 (53%). There was no difference in baseline characteristics among those who did and did not experience irAEs (Table). The most frequent irAEs were elevated AST/ALT (n = 7; 44%), rash (n = 4; 25%), and hypothyroid (n = 4; 25%). 3 G3 (rash and transaminitis) and 1 G4 AE (pured red cell apalasia) were observed. Among all pts, overall response rate (RR) and disease control rate (DCR) were 13 and 50%, respectively. Median progression free survival (PFS) and overall survival (OS) were 27 and 56 weeks (w), respectively. The RR and DCR were higher among irAEs vs non-irAEs, although this did not reach statistical significance (RR 25 vs 0%; p = 0.05; DCR 62 vs 35%; p = 0.19). Median PFS and OS were longer in those with irAEs vs non-irAE; PFS 33 vs 16 w (HR: 0.26; CI 95%: 0.076-0.89; p = 0.028); (OS 69 vs 21 w HR: 0.18; CI 95%: 0.05-0.58; p = 0.002). On multivariate analysis, viral etiology was associated with prolonged PFS (p = 0.002) and MELD was associated with reduced OS (p = 0.004). Conclusions: Development of irAEs was associated with prolonged PFS and OS in pts with HCC treated with nivolumab. Further study is needed to determine whether type of irAE, onset time, or duration affect cancer outcomes. [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.

Effect of BRAFV600E on response to sorafenib in advanced thyroid cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6002-6002 ◽  
Author(s):  
M. S. Brose ◽  
A. B. Troxel ◽  
M. Redlinger ◽  
K. Harlacker ◽  
C. Redlinger ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Progression Free Survival ◽  
Outcome Data ◽  
Rank Test ◽  
Open Label ◽  
Ki 67 ◽  
Kaplan Meier ◽  
Open Label Phase ◽  
Patient Will ◽  
Advanced Thyroid Cancer

6002 Background: We are conducting an open-label phase II study of sorafenib in patients with metastatic, iodine-refractory thyroid carcinoma. Methods: 55 Patients were administered sorafenib 400 mg orally BID. Responses were monitored by PET and CT. Primary endpoints were response rate (RR) and progression free survival (PFS) by RECIST criteria. BRAF and RAS mutation status is determined by DNA sequencing. Outcome data is evaluated using the Kaplan-Meier method and log-rank test. Biologic activity in tissue obtained during treatment at response and progression is being explored using immunohistochemistry (IHC) to pERK, pAKT and Ki-67 among others, in pretreatment blocks from virtually all patients, and a subset of 14 patients in whom on-treatment tissue is available. Results: We have completed accrual of the 55 patients planned for enrollment; median time on study is 34 weeks and 25 pts (45%) are male. Histological subtypes include papillary (PTC): 25 pts (47%); follicular/Hürthle Cell (FTC): 19 pts (36%); medullary: 4 pts (8%), and poorly differentiated/anaplastic: 5 pts (9%). 52/55 patients are evaluable for response at this time. Median PFS was 84 wks. Genotyping of BRAF is complete in 16 patients. For patients with PTC/FTC, the PFS for those with BRAFwt was 54 wks compared to 84+ wks for patients with BRAFV600E (p = 0.028). On-treatment tissue at progression demonstrates heterogeneity, with p-ERK and p-AKT suppressed in some areas, but highly expressed in others. Data at 6 months post accrual of the last patient will be presented along with patient thyroglobulin levels, PET and CT scans. IHC and additional genotyping will also be presented. Conclusions: Sorafenib has activity in patients with advanced thyroid cancer with an overall PFS of 84 wks. While most patients with PTC or FTC achieve durable responses, patients whose tumors harbor BRAFV600E have significantly longer PFS than those that are BRAFwt. [Table: see text]

scholarly journals Anlotinib in Chinese Patients With Recurrent Advanced Cervical Cancer: A Prospective Single-Arm, Open-Label Phase II Trial

2021 ◽  
Vol 11 ◽  
Author(s):  
Jun Zhu ◽  
Chunyan Song ◽  
Zhong Zheng ◽  
Lingfang Xia ◽  
Yanqiong Chen ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Phase Ii ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Chinese Patients ◽  
Cancer Center ◽  
Efficacy And Safety ◽  
Open Label ◽  
Open Label Phase

ObjectiveThis phase II, single-arm, prospective study aimed to evaluate the efficacy and safety of anlotinib in Chinese patients with recurrent or metastatic cervical cancer (CC).MethodsPatients with histologically proven recurrent or metastatic advanced CC were enrolled at Fudan University Shanghai Cancer Center. Patients received 12 mg of oral anlotinib daily before breakfast for 2 weeks of each 3-week (21 days) cycle separated by a 1-week interval. Anlotinib was administered orally until disease progression, patient withdrawal, intolerant toxicity, or death. The primary endpoint was the objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors, and the secondary endpoints included the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.ResultsBetween September 2018 and November 2019, 41 patients were recruited. The median age was 53 years old. The histological results revealed that 82.9% of the recruited patients had squamous cell carcinoma, 14.6% had adenocarcinoma, and 2.4% had other types. At the data cutoff date, six patients were still being treated, and 35 patients had discontinued treatment. Forty (40/41, 97.5%) patients were evaluated for treatment response. The median PFS and OS was 3.2 and 9.9 months, respectively, in patients who received anlotinib treatment. The ORR was 24.4%. In addition, 34.2% (14/41) of patients were confirmed to have stable disease, and 39.0% (16/41) of patients were confirmed to have progressive disease. The DCR was 58.5%. Ten patients (10/41) had a confirmed response during the follow-up period. Most adverse events (AEs) were grade 1 or 2. High-grade AEs (grade 3) included urinary leukocyte positivity (9.8%), hematuria (4.9%), and hypertension (2.4%).ConclusionThis is the first study to evaluate the efficacy and safety of anlotinib in Chinese patients with recurrent or metastatic CC. Anlotinib produced durable clinical responses with manageable safety in these patients.

Evaluation of different MET genotypes as biomarkers for immunotherapy outcomes in NSCLC patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21032-e21032
Author(s):  
Xuanzong Li ◽  
Linlin Wang
Keyword(s):  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Rank Test ◽  
Wild Type ◽  
Exact Test ◽  
Entire Cohort ◽  
Kaplan Meier ◽  
Tumor Mutational Burden ◽  
The Difference ◽  
Nsclc Patients

e21032 Background: Previous studies suggested that MET exon 14 ( METex14) mutation regarding as a distinct subset was sensitive to MET-inhibitors, but poorly response to immunotherapy. Conversly, MET non-exon-14 (non-ex14) mutations including those undetermined functions and affecting the kinase or extracellular domains were found to be associated with the resistance to MET-inhibitors. However, therapeutic strategies for MET-non-ex14 mutant cancer are still largely unknown, and the relationship between MET-non-ex14 mutations and the efficacy of immune checkpoint inhibitors (ICIs) has never been reported. Using two public ICIs-treated cohorts, we aimed to assess the role of MET mutations including both METex14 and MET-non-ex14 mutations in NSCLC patients undergoing ICIs therapy. Methods: A total of 385 ICIs-treated NSCLC patients were enrolled to our study. MET mutations were defined as any nonsynonymous mutations, and we divided them into METex14 and MET-non-ex14 mutation subsets according to the mutated-position on MET. Kruskal-Wallis test was used to analyze the difference of tumor mutational burden (TMB) score, and the Fisher’s exact test was applied to compare the rates of durable clinical benefit (DCB). Log-rank test was used to analyze the differences between Kaplan-Meier survival curves. Results: In the entire cohort, we found that 17 patients (17/385, 4.4%) had MET mutations, most of which were pure METex14 mutations (10/17, 58.8%). The median TMB of patients in the entire NSCLC cohort was 6.89 mut/Mb. MET-non-ex14 mutant patients (7/385, 1.8%) possessed a significantly higher TMB than METex14-mutant (10/385, 2.6%) and MET wild-type (368/385, 95.6%) sub-cohorts, respectively (median TMB, 17.92 mut/Mb versus 4.17 mut/Mb, p = 0.008; 17.92 mut/Mb versus 6.96 mut/Mb, p = 0.01, respectively). DCB was more common in patients harbored MET-non-ex14 mutations than patients with METex14 mutations and MET wild-type (66.7% versus 14.3%, p = 0.103; 66.7% versus 29.9%, p = 0.075, respectively). We found that patients with MET-non-ex14 mutations had a numerically longer progression free survival (PFS) than those with METex14 mutations and MET wild-type (p = 0.169). Moreover, the PFS was significantly longer in MET-non-ex14-mutant subgroup than patients with METex14 mutations (median PFS, 9.1 versus 2.1 months, p = 0.025). Correspondingly, the overall survival (OS) was significantly longer in MET-non-ex14-mutant subgroup than their wild-type counterparts (median OS, not reached versus 11 months, p = 0.039). Additionally, patients with MET-non-ex14 mutations exhibited relatively better OS versus METex14-mutant patients (median OS, not reached versus 18 months, p = 0.175). Conclusions: MET-non-ex14 mutations were associated with higher TMB, improved DCB rate, and could act as a favorable prognostic biomarker in ICIs-treated NSCLC patients.

Association of the neutrophil to eosinophil ratio with response to immunotherapy-based combinations in metastatic renal cell carcinoma.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 341-341
Author(s):  
Matthew D Tucker ◽  
Katy Beckermann ◽  
Kristin Kathleen Ancell ◽  
Kerry Schaffer ◽  
Renee McAlister ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Outcomes ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Rank Test ◽  
Cancer Center ◽  
Exact Test

341 Background: Neutrophilia is known to be associated with worse prognosis in metastatic renal cell carcinoma (mRCC); however, less is known about the role of eosinophils in the response to immunotherapy (IO). We investigated the association of the baseline neutrophil to eosinophil ratio (NER) with outcomes to IO-based combination treatment in mRCC. Methods: Patients with mRCC treated with ipilimumab plus nivolumab, pembrolizumab plus axitinib, or avelumab plus axitinib at the Vanderbilt-Ingram Cancer Center were retrospectively identified. Patients on >10mg prednisone and patients with prior IO were excluded. Baseline NER (at time of first IO) and association with progression free survival (PFS), overall survival (OS), and objective response rate (ORR) were investigated. Data cutoff was 9/1/2020. Analysis for PFS and OS was performed using the log-rank test and Mantel-Haenszel method, and analysis of the odds ratio for ORR was performed using Fischer’s exact test. Results: Sixty-one patients were identified: 89% clear cell histology, 74% prior nephrectomy, 69% IMDC intermediate risk, and 72% treatment-naïve. Patients with baseline NER < median (N=31) had improved clinical outcomes compared to patients with baseline NER > median (N=30) (Table). Improvement in PFS by NER was maintained when stratified by anti-PD-1/CTLA-4 and anti-PD(L)-1/VEGF (p= 0.0062 and p= 0.049); however, differences in OS and ORR were no longer significant. The median baseline NER among patients with partial response (PR) was significantly lower at 22.7 (95% CI 18.9-31.1) vs. 51.6 (95% CI 39.5-93.1) among those with progressive disease (PD) (p= 0.0054). For comparison, the median neutrophil to lymphocyte ratio was not significantly different between PR (2.60) and PD (3.84, p= 0.056). Conclusions: Patients with a low baseline NER treated with IO-based combinations had improved clinical outcomes compared to patients with a high baseline NER. Additional investigation of this parameter in larger cohorts is warranted. [Table: see text]

scholarly journals Apatinib plus camrelizumab (anti-PD1 therapy, SHR-1210) for advanced osteosarcoma (APFAO) progressing after chemotherapy: a single-arm, open-label, phase 2 trial

2020 ◽  
Vol 8 (1) ◽  
pp. e000798
Author(s):  
Lu Xie ◽  
Jie Xu ◽  
Xin Sun ◽  
Wei Guo ◽  
Jin Gu ◽  
...  
Keyword(s):  
Pulmonary Metastases ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Open Label Phase ◽  
High Grade Osteosarcoma

BackgroundResults of our previous study showed high objective response but short-term activity of apatinib in advanced osteosarcoma. We aimed to investigate the activity of apatinib in combination with camrelizumab in patients with inoperable high-grade osteosarcoma progressing after chemotherapy.MethodsThis open-label, phase 2 trial was conducted at Peking University People’s Hospital. We enrolled patients with advanced osteosarcoma progressed after chemotherapy. Patients received 500 mg apatinib orally once daily plus 200 mg camrelizumab by intravenous infusion every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) and clinical benefit rate at 6 months, which were based on RECIST V.1.1.Results43 patients were enrolled between January 25 and September 4, 2018. With median follow-up time of 48.3 (Q1, Q3, 30.6, 66.6) weeks, 13 (30.23%, 95% CI 17.2%, 40.1%) of 43 patients were progression free at 6 months and the 6-month PFS rate was 50.9% (95% CI 34.6%, 65.0%). Until final follow-up, the objective response rate was 20.9% (9/43) and two patients with durable disease control were observed. Patients with programmed cell death 1 ligand-1 (PD-L1) tumor proportion score ≥5% and pulmonary metastases tended to have a longer PFS in comparison to the others (p=0.004 and 0.017, respectively). Toxic effects led to dose reductions, or interruptions, or both in 24 (55.8%) of 43 patients and permanent discontinuation in 4 (9.3%) patients. There were no treatment-related deaths.ConclusionsAlthough the combination of apatinib and camrelizumab seemed to prolong PFS in comparison to single agent apatinib in treating advanced osteosarcoma, it did not reach the prespecified target of 6-month PFS of 60% or greater. Overexpression of PD-L1 and the presence of pulmonary metastases only were associated with longer PFS.Trial registration numberNCT03359018.

Efficacy and safety of sunitinib (SU) in patients (pts) with metastatic renal cell carcinoma (mRCC) and lung metastases (mets) only at baseline.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15098-e15098
Author(s):  
Nobuo Shinohara ◽  
Hideyuki Akaza ◽  
Yoshihiko Tomita ◽  
Takeshi Yuasa ◽  
Hiroyuki Fujimoto ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Objective Response ◽  
White Blood Cells ◽  
Progression Free Survival ◽  
Rank Test ◽  
Efficacy And Safety ◽  
Kaplan Meier ◽  
Common Grade ◽  
Hand Foot Syndrome ◽  
Grade 3

e15098 Background: The lungs may be the sole site of mets in RCC.In this retrospective analysis, we analyzed the efficacy and safety of SU in mRCC pts from a global phase (ph) III study and a Japanese ph II study who had lung mets only at baseline. Methods: In the ph III study, treatment (Tx)-naïve mRCC pts were randomized 1:1 to SU 50 mg/d on a 4-weeks-on-2-weeks-off schedule (n=375) or interferon-a (IFN) 9 MU subcutaneously TIW (n=360). In the single-arm ph II study, Tx-naïve (n=25) and cytokine refractory (n=26) mRCC pts received the same SU Tx. In the ph III study, progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan–Meier method, with median values compared by log-rank test. In both studies, objective response rate (ORR) was calculated with a two-sided 95% CI. PFS, OS, ORR, and safety were analyzed at final data cutoff. Results: In the ph III study, 31 (8%) and 42 (11%) pts in the SU and IFN groups, respectively, had lung mets only, compared with 12 (24%) in the ph II study. Baseline characteristics in lung mets pts were similar to all pts. In lung mets pts from the ph III study, ORR was higher with SU than with IFN (58.1% [95% CI: 39.1–75.5] vs. 19.0% [95% CI: 8.6–34.1]; P<0.001); there was a trend for longer median PFS with SU (14.1 vs. 7.8 months; HR: 0.531 [95% CI: 0.278–1.015]; P=0.0513); and median OS was comparable in both Tx subgroups (HR: 0.739 [95% CI: 0.335–1.628]; P=0.4507), although, at 25% of events, median OS was 22.9 months with SU vs. 15.8 months with IFN. In lung mets pts from the ph II study, ORR was 75.0% (95% CI: 42.8–94.5); at the time of analysis, median PFS and OS had not been reached; 4 pts (33%) had died due to any cause and 8 (67%) were alive without disease progression. The most common grade ≥3 SU-related AEs were fatigue, hand-foot syndrome, and diarrhea (all 19%) in the ph III study, and decreased platelets (100%), white blood cells (92%), and neutrophils (92%) in the ph II study. Conclusions: In the ph III study, Tx-naïve mRCC pts with lung mets only had significantly higher ORR and a trend for improved PFS and OS with SU compared with IFN. In the Japanese ph II study, ORR with SU was 75% in lung mets pts. Thus, 1st-line use of SU in mRCC pts with lung mets should be encouraged.

Final report of an open-label phase II trial of bevacizumab plus docetaxel and gemcitabine in metastatic, previously untreated nonsquamous non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18046-e18046
Author(s):  
Nathan A. Pennell ◽  
Sujith R. Kalmadi ◽  
Marc A. Shapiro ◽  
Hamed Daw ◽  
Cristina P. Rodriguez ◽  
...  
Keyword(s):  
Phase Ii ◽  
Advanced Nsclc ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Final Report ◽  
Hematologic Toxicity ◽  
Open Label ◽  
Open Label Phase

e18046 Background: Platinum and non-platinum doublet chemotherapy has similar efficacy in advanced NSCLC patients (pts). Bevacizumab (B) improves outcomes when added to platinum doublets, but its safety and efficacy in combination with non-platinum doublets is unknown. This study was designed to test the combination of B, docetaxel (D), and gemcitabine (G) in first-line treatment of advanced NSCLC. Methods: Pts with metastatic, non-squamous NSCLC, PS 0-1, and measurable disease by RECIST were enrolled in this open-label, single arm phase II trial. Pts received D (75 mg/m2) on d1, G (900 mg/m2) on d1 & 8, and B (15 mg/kg) on d1 every 21d for up to 6 cycles, followed by B maintenance until progression or 12 mos total. Pts received growth factor d9. CT scans were performed every 6 wks. The primary endpoint was 1-yr progression-free survival (PFS), with secondary endpoints of safety, objective response rate (ORR), overall PFS, and overall survival (OS). Pts with tumor cavitation, untreated brain metastases, and hemoptysis were excluded. Planned enrollment was 46. Results: 13 pts were enrolled from 12/2009 to 4/2011. Pt characteristics: Median age 63 (35-69), 85% male, PS 0 (38%), PS 1 (62%). The median # of cycles of chemotherapy was 6 (1-6), median # cycles of B was 4 (1-15), with 2 pts coming off study prior to the first evaluation (1 grade 5 encephalopathy, 1 grade 4 febrile neutropenia). 5 pts (38%) had chemo dose reduction and 4 (31%) discontinued treatment for toxicity. 3 pts (23%) discontinued B prior to progression, 2 for tumor cavitation and 1 for grade 1 hemoptysis. The grade 3-5 non-hematologic toxicity rate was 69%, with 6 pts (46%) hospitalized with pneumonitis/pneumonia felt possibly related to study drugs. At this point enrollment was halted for safety concerns. The 1-yr PFS was 8%, and the median PFS was 6.9 mos (95% CI 2.0-NYR). 11 pts were evaluable for response, and 6 pts had partial responses for an ORR of 55%. The median OS was NYR with median follow up of 10.9 mos. Conclusions: The combination of B, D, and G was not tolerable at the doses and schedule used in this study. A formal phase I trial is needed if this combination is to be investigated further.

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