Heterogeneity of intermediate prognosis patients (pts) with metastatic renal cell cancer (mRCC) treated with sunitinib.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 446-446
Author(s):  
Avishay Sella ◽  
M. Dror Michaelson ◽  
Ewa M. Matczak ◽  
Ronit Simantov ◽  
Mariajose Lechuga ◽  
...  
Keyword(s):  
Risk Factors ◽  
Kinase Inhibitors ◽  
Risk Model ◽  
Cox Regression ◽  
Performance Status ◽  
Cell Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cancer Center ◽  
Ecog Performance Status

446 Background: The Memorial Sloan Kettering Cancer Center risk model (MSKCC) stratifies pts with mRCC into 3 prognostic groups based on 5 risk factors. The Intermediate Prognosis (INTMP) risk group is characterized by the presence of 1 or 2 factors, equivalent to 15 possible distinct entities. This heterogeneity suggests that the efficacy of tyrosine kinase inhibitors may be less predictable in the INTMP than in the other groups. Methods: We identified 548 patients with INTMP mRCC from a pooled analysis of patients treated with sunitinib in 6 prospective phase II and III clinical trials. Statistical analysis was performed using Cox regression and Kaplan-Meier methods and Pearson chi-square tests. Results: Most INTMP pts were male (69%), with clear cell carcinoma (93%), good ECOG performance status (PS) (60.5% PS 0; 38% PS 1; 1.5% PS 2) and median age 60. There were 325 pts (56%) with 1risk factor, and the most common were <1 year from diagnosis (38%); low hemoglobin (Hg) (29%), or both (16%). Objective response rate (RR) was 35.4%, progression free survival (PFS) was 8.4 months (m) and overall survival (OS) was 20.5 m. The 325 (59.3%) pts with one risk factor fared better than the 223 (40.7%) patients with two: PFS 10.7 vs 6.5 m, HR 0.684(95% CI 0.563-0.832, p<0.001); OS 26.3 vs 14.1 m, HR 0.522 (95% CI 0.420-0.648, p<0.001). RR was similar (38.5% vs 30.9%, p=0.071). Sunitinib was more effective in pts with PS 0: PFS 9.7 vs 7.8 m, HR 0.797 (95% CI 0.654-0.972, p=0.0242); OS 24.7 vs 14.0 m, HR 0.529 (95% CI 0.426-0.657, p<0.001), RR 38.9% vs 30.1%, (p=0.036). The most common grade 3/4 adverse events (AE) were fatigue (17%), hypertension (10%), hand foot skin reaction (9%), and nausea (4%). Overall, 17% of patients discontinued due to AE, and the overall pattern of AEs did not vary among the subgroups. Conclusions: MSKCC INTMP is a heterogeneous group comprised mostly of pts with low Hg and/or < 1 year from diagnosis. PFS and OS are superior in pts with 1 vs. 2 risk factors, and PS is also an important factor in the INTMP group. Sunitinib is active and well-tolerated in INTMP pts. Clinical trial information: NCT00077974, NCT00083889, NCT00137423, NCT00267748, NCT00338884, NCT00054886.

Cisplatin (CDDP) and radiation versus cetuximab (Cx) and radiation in locally advanced head and neck squamous cell cancer (SCHNC): A retrospective review.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16009-e16009 ◽  
Author(s):  
Prakash Peddi ◽  
Runhua Shi ◽  
Lori Panu ◽  
Fred Ampil ◽  
Cherie-Ann Nathan ◽  
...  
Keyword(s):  
Performance Status ◽  
Cell Cancer ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Rank Test ◽  
Cancer Center ◽  
Ecog Performance Status ◽  
Chi Square ◽  
Group A

e16009 Background: SCHNC is a common malignancy and approximately 60% of patients present with locally advanced disease. There is paucity of data directly comparing Cx and CDDP with concurrent radiation in locally advanced SCHNC. We retrospectively reviewed charts of patients treated with CDDP and/or Cx along with radiation in locally advanced SCHNC comparing efficacy and outcomes in an academic cancer center. Methods: Ninety-five patients with locally advanced SCHNC were treated with concurrent CDDP (100 mg/m2 day 1, 22, 43) or Cx (400mg/m2 on day -7 and 250mg/m2 weekly) at our institution between January 2006 and June 2011. Forty-four patients were treated with CDDP (group A), 24 with Cx (group B) and 27 were initially started on CDDP but were switched to Cx secondary to toxicity (group C). All patients received concurrent radiation treatments (66-70 Gy, 2.0 Gy/fraction). The selection of CDDP versus Cx was largely based on ECOG performance status (PS) and baseline renal function of the patients. Chi-square test, analysis of variance, and log-rank test was used for analysis. The three groups had similar baseline characteristics except for mean age of 61, 56 and 55 years in group A, B and C respectively; T4 tumors consisted of 44%, 75% and 41% in groups A, B and C respectively. Groups A, B and C had a combined ECOG 0 and I (PS) of 93%, 75% and 92%. Patients with ECOG III PS were excluded. Results: Oropharynx was the most common treated site (38%) followed by Larynx (35%). Complete response (CR) was seen in 77%, 17% and 67% in groups A, B and C respectively (P<0.001). Median progression free survival (PFS) was 16.6, 4.3 and 22.8 in groups A, B and C respectively (P<0.001) and median overall survival (OS) was >35, 11.6 and >32 months in groups A, B and C respectively (P<0.0001). Conclusions: Concurrent CDDP with radiation leads to better response rate PFS and OS as opposed to Cx though many patients treated with CDDP could not complete treatment due to toxicity. Randomized trial comparing the two should be considered.

Clinical outcomes model in renal cell cancer patients treated with modified vaccinia Ankara plus tumor-associated antigen 5T4

2015 ◽  
Vol 30 (1) ◽  
pp. 111-121 ◽  
Author(s):  
Robert J. Amato ◽  
Youxin Xiong ◽  
Hui Peng ◽  
Virginia Mohlere
Keyword(s):  
Renal Cell Cancer ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Performance Status ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Elispot Response ◽  
Ecog Performance Status ◽  
Fuhrman Grade ◽  
Phase Ii Studies

Aims We developed an outcomes model to select patients for renal cell cancer vaccine immunotherapy. Materials and methods We examined clinical data from 2 phase II studies of modified vaccinia Ankara as vector to express 5T4 (MVA-5T4), calculated progression-free survival (PFS) and overall survival (OS), and created risk groups based on the number of factors involved. Results Median OS was 12.4 months; median PFS was 3.6 months. Significant factors (p<0.05) included neutrophils (both), bone metastases (OS), ECOG performance status (OS), lactate dehydrogenase levels (both), prior therapy with tyrosine kinase inhibitors plus immunotherapy (OS), Fuhrman grade (OS), and 5T4-specific ELISPOT response (PFS). By group, median OS was not reached in patients with favorable risk (censored at cutoff), was 13.7 months in those with intermediate risk and 4.0 months in those with poor risk. Conclusions Further validation of this model will identify the patients most likely to respond to MVA-5T4 and provide a framework for outcomes models for other vaccine therapies.

Safety and efficacy of axitinib in pretreated patients with metastatic renal cell carcinoma: A single center experience of the Medical University of Vienna, Austria.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15535-e15535
Author(s):  
Ursula Maria Vogl ◽  
Lothar Ponhold ◽  
Gottfried J Locker ◽  
Christoph Zielinski ◽  
Christoph Klingler ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Renal Cell ◽  
Performance Status ◽  
Cell Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Second Line ◽  
Ecog Performance Status ◽  
Single Center Experience ◽  
Metastatic Sites

e15535 Background: Axitinib is a highly selective inhibitor of VEGFR-1, 2 and 3 and has recently been approved for second-line treatment of metastatic renal cell cancer (mRCC). We present data of 43 patients treated with axitinib in second-line and beyond. Methods: Medical records of all patients who were treated with axitinib between July 2009 and December 2012 were retrospectively reviewed. Axitinib was prescribed at a dose of 5 mg bid and escalated to 7 or 10 mg bid in the absence of hypertension and other dose-limiting toxicities. Objective response rate (ORR) was assessed by RECIST. Progression free survival (PFS) and overall survival (OS) were calculated from the first day of axitinib until progression and/or death, respectively. Results: Fourty-three patients with a median age of 65 years (range: 17-84) are currently evaluable for analysis. The majority of patients (58.1%) had an ECOG Performance status of 0 and were classified MSKC- intermediate risk (62.8%). All patients had undergone surgery for the primary tumor and 53.5% had three or more metastatic sites. Fifty-five percent of the patients received axitinib in third or fourth-line (14% and 41.9%, respectively). Prior therapies included sunitinib (86%), everolimus (35%) and pazopanib (35%) and 62.8% had progressed on sunitinib before axitinib was initiated. Objective remission and disease stabilization were observed in 14.3% and 40% of the entire population. The median PFS and OS were 6.8 months (95% CI: 5.5 – 8.0) and 17.2 months (95% CI: 10.8 – 23.6), respectively. Dose escalation to 7 or 10 mg bid was feasible in 40% of the patients. Fatigue (76.7%), hypertension (65.1%) and hypothyroidism (53.5%) were among the most commonly observed all grade toxicities. Conclusions: Axitinib showed considerable efficacy in both second-line and beyond second-line patients. Generous dose escalation based on a “treat to hypertension”-concept may have led to a longer PFS than previously reported from a purely VEGFR-TKI-refractory patient population.

Peritoneum metastasis (PM) as a prognostic factor in metastatic gastric cancer (MGC) treated with anti-PD-1/PD-L1 monotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3051-3051 ◽  
Author(s):  
Yukiya Narita ◽  
Keiji Sugiyama ◽  
Seiichiro Mitani ◽  
Kazunori Honda ◽  
Toshiki Masuishi ◽  
...  
Keyword(s):  
Cox Regression ◽  
Negative Impact ◽  
Performance Status ◽  
Univariate Analysis ◽  
Objective Response ◽  
Metastatic Gastric Cancer ◽  
Cancer Center ◽  
Ecog Performance Status ◽  
Cox Regression Analysis ◽  
Line Therapy

3051 Background: Anti-PD-1 monotherapy has proven effective for the patients (pts) with MGC. However, the identification of biomarkers for predicting clinical outcomes remain as critical needs. We aimed to identify baseline characteristics associated with time to treatment failure (TTF) or overall survival (OS) for anti-PD-1/PD-L1 monotherapy as second- or later-line therapy in MGC. Methods: Routine blood count parameters and clinical characteristics at baseline were retrospectively investigated in 31 pts with MGC in Aichi Cancer Center Hospital. Endpoints were TTF and OS following anti-PD-1/PD-L1 monotherapy. Kaplan-Meiyer and Cox regression analysis were applied for survival analyses. Results: Patient characteristics were as follows: median age (range), 68 (47–83); ECOG performance status (PS) 0/1, 21/10; PM +ve/-ve, 12/19; No. of metastatic sites 1–2/≥3, 18/13; No. of prior chemotherapy regimens 1–2/≥3, 11/20; and absolute eosinophil count (AEC) <150/≥150 /μl, 14/17. Objective response rate and disease control rate (RECIST ver. 1.1) were 26% vs. 0% (odds ratio [OR], 3.76; P = 0.12) and 79% vs. 50% (OR, 3.58; P = 0.12) in the PM -ve group (Cohort A) and the PM +ve group (Cohort B), respectively. On univariate analysis, the pts with poor PS, PM +ve, and high AEC were significantly poor TTF; and poor PS and PM +ve were significantly identified as prognostic factors of poor OS. On multivariate analysis, only PM +ve was independent negative impact not only for TTF but also for OS. Median TTF and OS were 5.4 vs. 1.3 months (M) (adjusted hazard ratio [HR], 4.29; 95%CI, 1.60–11.5; P < 0.01) and 28.2 vs. 7.5 M (adjusted HR, 3.68; 95%CI, 1.25–10.8; P = 0.02) in Cohort A and Cohort B. Six-months TTF probabilities of 42% vs. 0% ( P = 0.03) and one-year OS probabilities of 58% vs. 8% ( P< 0.01) were observed in Cohort A compared to in Cohort B. Conclusions: PM -ve in the pts treated with anti-PD-1/PD-L1 monotherapy was associated with better efficacy. In the pts with PM -ve, anti-PD-1/PD-L1 monotherapy could be adapted in first-line therapy. [Table: see text]

Phase Ib safety trial of CVX-060, an intravenous humanized monoclonal CovX body inhibiting angiopoietin 2 (Ang-2), with axitinib in patients with previously treated metastatic renal cell cancer (RCC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2533-2533
Author(s):  
Ashwin Gollerkeri ◽  
Michael S. Gordon ◽  
John M. Burke ◽  
Ralph Hauke ◽  
Jiri Tomasek ◽  
...  
Keyword(s):  
Phase Ii ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Performance Status ◽  
Cell Cancer ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Ecog Performance Status ◽  
Prior Therapy

2533 Background: PF-04856884 is a recombinant humanized monoclonal antibody fused to two Ang-2 binding peptides. Axitinib is a potent and selective second-generation inhibitor of vascular endothelial growth factors (VEGFs) that is approved for patients (pts) with advanced renal cell cancer who failed 1 prior therapy. Metastatic RCC (mRCC) is an angiogenic tumor sensitive to VEGF tyrosine kinase inhibitors. Resistance to VEGF targeted therapy may be mediated by Ang-2. Methods: In Part I (safety lead in) of the study, the primary endpoint was treatment related dose limiting toxicities (DLT) in pts with mRCC who had received 1-3 prior treatments. Pts received PF-04856884 (15 mg/kg/week) plus axitinib (5 mg BID) for 4 week cycles (the recommended Phase II dose of each) and were assessed for DLT, PK, and potential predictive biomarkers (Ang-2 and VEGF-A). For Part II (Phase II portion), pts with mRCC who had received 1 prior anti-VEGF agent were to be randomized to PF-04856884 + axitinib or axitinib alone to assess median progression free survival. Results: Part I enrolled 18 pts with median age of 62.5 years (39-82), and ECOG performance status of 0-1. One pt had a DLT of Grade 4 pulmonary embolism (PE). Most common related AEs: anorexia in 10 pts (56%), diarrhea 8 (44%), fatigue 8 (44%), nausea 7 (39%), hypertension 6 (33%) and vomiting 6 (33%). Treatment-related thromboembolic events (TEEs) were observed: PE in 2 pts (11%), and cerebrovascular accident (CVA), presumed bowel ischemia, and possible cardiac chest pain in 1 pt (6%) each. One pt had Grade 2 venous thrombosis unrelated to either treatment. Due to the reported TEE, PF-04856884 was reduced to 10 mg/kg in pts remaining on study and enrollment to Part II was not initiated. No significant PK interaction was observed. Two pts had partial response (PR) and 1 pt had unconfirmed PR. Twelve pts (66%) remained on study ≥91 days with a median duration of 120 days (8-279). Anti-PF-04856884 antibody results are not available. Conclusions: Due to the higher than expected TEEs, alternate doses of PF-04856884 and/or disease settings are being considered. Clinical trial information: NCT01441414.

MAVERICC, a phase 2 study of mFOLFOX6-bevacizumab (BV) vs FOLFIRI-BV with biomarker stratification as first-line (1L) chemotherapy (CT) in patients (pts) with metastatic colorectal cancer (mCRC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 493-493 ◽  
Author(s):  
Heinz-Josef Lenz ◽  
Fa-Chyi Lee ◽  
Linda Yau ◽  
Han A. Koh ◽  
James A. Knost ◽  
...  
Keyword(s):  
Cox Regression ◽  
Performance Status ◽  
Objective Response ◽  
Hepatic Metastases ◽  
Progression Free Survival ◽  
Metastatic Lesion ◽  
Phase 2 ◽  
Open Label ◽  
Ecog Performance Status ◽  
Phase 2 Trial

493 Background: Standard 1L mCRC treatment (tx) includes a CT backbone (e.g., modified leucovorin [LV]/5-fluorouracil [5-FU]/oxaliplatin [mFOLFOX6] or LV/ 5-FU/ irinotecan [FOLFIRI]) and biologic therapy (e.g., BV). The preferred CT backbone for anti VEGF tx is unknown. MAVERICC (NCT01374425), a global, randomized, open-label, phase 2 trial, assessed tx efficacy and safety of mFOLFOX6-BV vs FOLFIRI-BV in pts with mCRC. Intratumoral ERCC1 and plasma VEGF-A were studied as biomarkers for oxaliplatin- and BV-containing tx, respectively. Methods: Pts with mCRC (≥1 measurable metastatic lesion, ECOG performance status ≤1) were randomized 1:1 to receive BV (5 mg/kg) + mFOLFOX6 or FOLFIRI every 2 weeks, stratified by ERCC1 level (low [£1.7] vs high [>1.7]) and region. VEGF-A levels were measured at baseline. Primary objectives were to evaluate: ERCC1 as a biomarker of progression-free survival (PFS) in 1L mCRC tx (mFOLFOX-BV vs FOLFIRI); and VEGF-A as a biomarker for BV and as a biomarker in combination with ERCC1 for PFS following CT + BV. Secondary objectives were to evaluate: the effect of ERCC1 and VEGF-A on overall survival (OS), objective response rate, hepatic metastases resection, and safety. PFS and OS were estimated by Kaplan–Meier methods, hazard ratios (HR) were estimated by Cox regression, and p-values were based on stratified log-rank tests. ERCC1 biomarker analyses are presented here. Results: A total of 376 pts were randomized: median age, 61 yr; white race, 83%; US region, 85%. Baseline characteristics: ERCC1 high, 35%; KRAS mutant, 34%. Efficacy results are shown (see Table). Conclusion: Consistent with previous findings, PFS and OS were comparable in pts treated with either 1L mFOLFOX6-BV or FOLFIRI-BV. Exploratory analyses within pts with high ERCC1 levels suggest consistent results. VEGF-A analyses are ongoing. Clinical trial information: NCT01374425. [Table: see text] [Table: see text]

First-line nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients with advanced non-small cell lung cancer (NSCLC): Two-year update from CheckMate 9LA.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9000-9000
Author(s):  
Martin Reck ◽  
Tudor-Eliade Ciuleanu ◽  
Manuel Cobo ◽  
Michael Schenker ◽  
Bogdan Zurawski ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Performance Status ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Expression Level ◽  
First Line ◽  
Ecog Performance Status ◽  
Grade 3

9000 Background: In the randomized phase 3 CheckMate 9LA trial (NCT03215706), first-line NIVO + IPI combined with 2 cycles of chemo significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs chemo alone (4 cycles). Clinical benefit was observed regardless of programmed death ligand 1 (PD-L1) expression level and histology. Here we report data with 2 years’ minimum follow-up from this study. Methods: Adult patients (pts) with stage IV / recurrent NSCLC, ECOG performance status ≤ 1, and no known sensitizing EGFR/ALK alterations were stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous) and were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles; n = 361) or chemo alone (4 cycles; n = 358). Pts with non-squamous NSCLC in the chemo-alone arm could receive pemetrexed maintenance. The primary endpoint was OS. Secondary endpoints included PFS and ORR by blinded independent central review, and efficacy by different PD-L1 levels. Safety was exploratory. Results: At a minimum follow-up of 24.4 months for OS (database lock: Feb 18, 2021), pts treated with NIVO + IPI + chemo continued to derive OS benefit vs chemo, with a median OS of 15.8 months vs 11.0 months, respectively (HR, 0.72 [95% CI, 0.61–0.86]); 2-year OS rates were 38% vs 26%. Median PFS with NIVO + IPI + chemo vs chemo was 6.7 months vs 5.3 months (HR, 0.67 [95% CI, 0.56–0.79]); 8% and 37% of pts who had disease progression received subsequent immunotherapy, respectively. ORR was 38% with NIVO + IPI + chemo vs 25% with chemo. Similar clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across the majority of subgroups, including by PD-L1 expression level (Table) or histology. Any grade and grade 3–4 treatment-related adverse events were reported in 92% and 48% of pts in the NIVO + IPI + chemo arm vs 88% and 38% in the chemo arm, respectively. Conclusion: With 2 years’ minimum follow-up, first-line NIVO + IPI + chemo demonstrated durable survival and benefit versus chemo in pts with advanced NSCLC; no new safety signals were identified. Clinical trial information: NCT03215706. [Table: see text]

scholarly journals Real-world efficacy and safety of liposomal irinotecan plus fluorouracil/leucovorin in patients with metastatic pancreatic adenocarcinoma: a study by the Korean Cancer Study Group

2019 ◽  
Vol 11 ◽  
pp. 175883591987112 ◽  
Author(s):  
Changhoon Yoo ◽  
Hyeon-Su Im ◽  
Kyu-pyo Kim ◽  
Do-Youn Oh ◽  
Kyung-Hun Lee ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Real World ◽  
Performance Status ◽  
Objective Response ◽  
Real Life ◽  
Progression Free Survival ◽  
Real World Data ◽  
Ecog Performance Status ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Liposomal Irinotecan

Background: Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) was effective and well-tolerated in patients with metastatic pancreatic adenocarcinoma (mPAC) that progressed on gemcitabine-based therapy in the global NAPOLI-1 trial. Real-world data may further clarify the outcomes and safety profile of nal-IRI + 5-FU/LV in clinical practice. Methods: This retrospective analysis included patients with mPAC who received nal-IRI + 5-FU/LV following gemcitabine-based therapy under a Managed Access Program in Korea. Results: From January 2017 to April 2018, 86 patients across 10 institutions received nal-IRI + 5-FU/LV (median age, 61 years; 60% male; ECOG performance status, 0–1). A total of 35 (41%) and 51 (59%) patients had received less than two and two or more lines of chemotherapy before inclusion, respectively. At a median follow up of 6.4 months, median overall survival (OS) was 9.4 months (95% confidence interval [CI] 7.4–11.4) and median progression-free survival (PFS) was 3.5 months (95% CI 1.3–5.7). Six-month OS and PFS rates were 65.1% and 37.5%, respectively. Objective response and disease control rates were 10% and 55%, respectively. Most common grade 3–4 toxicities were neutropenia (37.2%), nausea (10.5%), vomiting (9.3%), anorexia (8.1%) and diarrhoea (4.7%). Conclusion: Real-life data for Korean patients indicate that, consistent with NAPOLI-1, nal-IRI + 5-FU/LV is effective and well-tolerated in patients with mPAC that progressed on gemcitabine-based therapy.

Phase II efficacy and safety study of nintedanib versus sunitinib in previously untreated renal cell carcinoma (RCC) patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4506-4506 ◽  
Author(s):  
Tim Eisen ◽  
Yaroslav Shparyk ◽  
Robert Jones ◽  
Nicholas James MacLeod ◽  
Graham Temple ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Qtc Interval ◽  
Efficacy And Safety ◽  
Ecog Performance Status ◽  
Interval Change ◽  
First Line Therapy

4506 Background: Sunitinib (S) is established as a standard first-line therapy for patients (pts) with advanced RCC. However, treatment can be limited by the occurrence of drug-related adverse events (AEs). This Phase II study assessed the efficacy and safety of nintedanib (N) – a potent, triple angiokinase inhibitor of VEGFR-1–3, PDGFR-α/β, and FGFR-1–3, as well as RET and Flt3 – vs S in previously untreated pts with RCC. Methods: Ninety-nine eligible pts (96 of whom were treated) with advanced, unresectable/recurrent clear cell RCC, an ECOG performance status of 0–1, and no prior systemic therapy were randomized 2:1 to receive N 200 mg twice daily (n=64; given in 4-week cycles) or S 50 mg once daily (n=32; 4 weeks on, 2 weeks off schedule). Treatment continued until disease progression or unacceptable drug-related AEs. Primary endpoints were progression-free survival at 9 months (PFS-9) and, in N-treated pts only, QTc interval change (baseline to day 15). Secondary endpoints included PFS, objective response rate (ORR; RECIST 1.1), overall survival (OS), time to progression (TTP), time to treatment failure (TTF), and AEs. Results: Baseline characteristics were balanced between the arms. PFS-9 was not statistically significantly different between N- and S-treated pts (43 vs 45%; p=0.85). There were also no statistically significant differences between N and S with regard to PFS (median: 8.44 vs 8.38 mo; hazard ratio: 1.16; 95% CI: 0.71–1.89; p=0.56), confirmed ORR (18.8 vs 31.3%; p=0.19), OS (median: 20.37 vs 21.22 mo; p=0.63), TTP (median: 8.48 vs 8.54 mo; p=0.52), and TTF (median: 8.41 vs 8.36 mo; p=0.46). Grade ≥3 AEs occurred in 47% of N-treated pts and 56% of S-treated pts. Common AEs (all grades; N vs S) included diarrhea (61 vs 50%), nausea (38 vs 34%), fatigue (both 25%), and vomiting (16 vs 22%). Dermatologic AEs (8 vs 47%) were less frequent with N than S. There was no increase from baseline in QTc >60 ms on days 1 or 15 in N-treated pts, and there was no relationship between N exposure and QT interval change. Conclusions: N demonstrated similar efficacy to S and had a manageable safety profile, including a lower incidence of dermatologic AEs vs S. In addition, N was not associated with QT prolongation. Clinical trial information: NCT01024920.

Patterns of referral to palliative care in clinical practice in patients with stage IV non-small cell lung cancer.

2013 ◽  
Vol 31 (31_suppl) ◽  
pp. 39-39
Author(s):  
Safiya Karim ◽  
Shahid Ahmed
Keyword(s):  
Palliative Care ◽  
Clinical Practice ◽  
Cox Regression ◽  
Smoking Status ◽  
Performance Status ◽  
Stage Iv ◽  
Cancer Center ◽  
Ecog Performance Status ◽  
Logistic Regression Models ◽  
Symptomatic Disease

39 Background: Recent evidence has shown that patients with stage IV NSCLC benefit from early referral to palliative care (PC). In August 2010, a landmark randomized control trial revealed that patients with advanced NSCLC, who received early PC, had better quality of life, mood and survival (NEJM 2010; 363:733-42). Our study aimed to determine pattern of PC referral in clinical practice, in patients with stage IV NSCLC before and after the publication of the trial, and to assess factors correlated with PC referral. Methods: The study population was comprised of a cohort of patients with stage IV NSCLC, diagnosed between 2009 and 2011, and referred to the Saskatoon Cancer Center. Logistic regression models were used to assess factors correlated with PC referral. Kaplan Meier method was used to estimate survival. Cox regression analyses were used to determine factors correlated with survival. Results: 215 patients with median age of 68 yrs (range: 40-92) and M:F of 108:107 were identified. 101 (47%) patients had comorbid illness, 100 (47%) had ECOG performance status <2, 136 (63%) were married/common law and 161 (75%) had symptomatic disease. 126/251 (58%) were referred to PC. 70/118 (59%) diagnosed before Sep 2010 were referred to PC compared with 56/97 (58%) diagnosed after Sep 2010 (p=NS). The median time to PC referral from date of diagnosis was 51 days (inter-quartile range: 19-155). 33% patients were referred within 4 wks of diagnosis. Symptomatic disease (odd ratio [OR]=3.7, 95% CI =1.8-7.5), bone metastasis (OR = 3.0, 95% CI = 1.6-5.6), and brain metastasis (OR=2.2, 95% CI =1.1-4.5) were correlated with referral to PC. Median survival of whole cohort was 4 months (95% CI: 3.1-4.8). 2nd or 3rd line therapy (Hazard ratio [HR]= 0.54, 95% CI:0.34-0.87), non-smoking status (HR= 0.58, 95% CI:0.38-0.87), chemotherapy (HR 0.64, 95% CI:0.46-0.89), and lack of symptoms (HR=0.68, 95%CI:0.48-0.96) were correlated with better survival. Conclusions: Our study shows that publication of the landmark trial did not influence the pattern of referral to PC at our center. Symptomatic patients and those with metastasis to brain or bone were more often referred to PC. No survival benefit was seen in patients who were referred to PC.

Sign in / Sign up

Export Citation Format

Share Document