scholarly journals Clinical Prognostic Factors in Patients With Metastatic Adrenocortical Carcinoma Treated With Second Line Gemcitabine Plus Capecitabine Chemotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Salvatore Grisanti ◽  
Deborah Cosentini ◽  
Marta Laganà ◽  
Alessandra Morandi ◽  
Barbara Lazzari ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Clinical Benefit ◽  
Performance Status ◽  
Progression Free Survival ◽  
Advanced Lung Cancer ◽  
Second Line ◽  
Ecog Performance Status ◽  
Heavily Pretreated ◽  
Node Metastases ◽  
And Performance

Gemcitabine plus Capecitabine (Gem/Cape) is a frequently adopted second line chemotherapy for metastatic adrenocortical carcinoma (ACC), but only a minority of patients is destined to obtain a clinical benefit. The identification of baseline predictive factors of efficacy is relevant. We retrospectively analyzed clinical data from 50 consecutive patients with metastatic progressing ACC treated between 2011 and 2019. Patients received intravenous Gemcitabine and oral Capecitabine on a metronomic schedule. Previous mitotane therapy was maintained. Clinical benefit (partial response + stable disease) at 4 months was 30%, median progression-free survival (PFS) and disease-specific survival (DSS) from Gem/Cape start were 3 and 8 months, respectively. Among clinical variables evaluated before the start of Gem/Cape, presence of ECOG performance status ≥1 [HR 6.93 95% confidence interval (CI) 0.03–0.54, p.004] and neutrophil-to-lymphocyte ratio (NLR) ≥5 [HR 3.88, 95% (CI) 0.81–0.90, p.003] were independent indicators of poor PFS at multivariate analysis. Conversely, surgery of primary tumor, the presence of lung or lymph-node metastases, blood mitotane level, anemia, and the Advanced Lung cancer Inflammation index (ALI) failed to be independently associated. This study confirms that the Gem/Cape schedule is modestly active in heavily pretreated ACC patients (28% received at least two previous chemotherapy lines). NLR and performance status (PS) are easily available clinical parameters that are helpful to identify patients not likely to derive significant advantage from Gem/Cape chemotherapy.

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]

Efficacy of weekly paclitaxel-bevacizumab combination in advanced nonsquamous non-small cell lung cancer (NSCLC): AVATAX, a retrospective multicentric study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21086-e21086
Author(s):  
Geoffroy Bilger ◽  
Anne-Claire Toffart ◽  
Marie Darasson ◽  
Michaël Duruisseaux ◽  
Lucie Ulmer ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
Multicentric Study ◽  
Significant Difference ◽  
Third Line ◽  
And Performance ◽  
Line Setting

e21086 Background: With the growing role of immunotherapy (ICI) as first-line setting for advanced NSCLC, strategies must be redefined after failure. The combination paclitaxel-bevacizumab showed in the ULTIMATE trial a significant superiority versus docetaxel as second or third-line treatment. Limited restropective studies has demonstrated unexpected efficacy of chemotherapy after prior progression on ICI. This combination could be use as salvage treatment following ICI. Methods: This multi-centric retrospective study identifies patients treated with the combination paclitaxel-bevacizumab in metastatic non-squamous NSCLC as second-line therapy or beyond. Main objectives were to describe safety and efficacy of this combination, with a special attention to the sub-group treated just after ICI. Results: From January 2010 to February 2020, 314 patients started the paclitaxel-bevacizumab combination : 55% male, with a median age of 60 years, 27% with a performance status ≥2, 45% with brain metastases. A majority of patients were treated in second (20%) and third-line (39%), and 28% were treated just after ICI failure (88/314). Objective response rate (ORR) was 40% and disease control rate was 77 %. Median progression-free survival (PFS) and overall survival (OS) were 5,7 months [IQ,3,2–9,6] and 10,8 months [IQ,5,3–19,6] respectively. All grades adverse events concerned 82% of patients, including 53% asthenia and 39% neurotoxicity, and 25% of patients continued a monotherapy alone due to toxicity. Median PFS for patients treated after ICI failure (ICI+) was significantly superior compare to those not previously treated with ICI (ICI-) : 7,0 months [IQ,4,2–11,0] vs 5,2 months [IQ,2,9–8,8] p (log-rank) = 0,01. There was not statistically significant difference in term of OS between this two groups. In multivariate analysis, factors associated with superior PFS were previous ICI treatment (ICI+) and performance status. Conclusions: This study confirms an acceptable toxicity profile associated with interesting efficacy of the combination paclitaxel-bevacizumab as second-line treatment or beyond for non–squamous NSCLC patients, particularly after progression with ICI.

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.

Prognostic score for second or further line immunotherapy in advanced non-small cell lung cancer (aNSCLC): An external validation.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14077-e14077
Author(s):  
Arsela Prelaj ◽  
Giuseppe Lo Russo ◽  
Claudia Proto ◽  
Diego Signorelli ◽  
Roberto Ferrara ◽  
...  
Keyword(s):  
Prognostic Score ◽  
Performance Status ◽  
External Validation ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Second Line ◽  
Ecog Performance Status ◽  
Prognostic Groups ◽  
Recorded Data ◽  
Ecog Ps

e14077 Background: Beyond PD-L1, nowadays oncologists can only use clinical characteristics to candidate patients for immunotherapy (IO). Previously, a clinical prognostic score composed by ECOG performance status (PS), sex, histology, stage, uses of platin-based therapy at first-line (1L) and response to 1L categorized 3 different prognostic groups for patients treated with second-line (2L) chemotherapy (CHT) (Di Maio, EJC. 2010 Mar;46(4):735-43.). The aim of this study is to assess if the same score is able to discriminate the outcome of aNSCLC pts treated in 2L or further-line IO, potentially helping decision making. Methods: We recorded data of patients collected from two institutional databases: Istituto Nazionale Tumori of Milan and IRCCS Oncologico Giovanni Paolo II of Bari, Italy. Overall survival (OS) was the primary endpoint and also progression-free survival (PFS) was assessed. Prognostic score was generated, and pts were divided into 3 prognostic groups: best (B: < 5), intermediate (I:5-9), worst (W: > 9). Results: Overall, 347 pts were included in the analysis (193 from Milan and 154 from Bari). Median age was 66 years (y) (30 – 88y), most were < 70 y (67.5%), male (70.7%), smokers (79.5%) and adenocarcinoma (74.6%). ECOG PS was: 0 (23%), 1 (54.5%) and 2 (22.5%). Pts distribution was: 28%, 51% and 21% in the B, I and W groups, respectively. Median OS was 18.0 months for B group, 8.5 months for I group (HR vs B 1.83, 95%CI 1.35 – 2.47, p < 0.001) and 2.6 months for W group (HR vs B 5.77, 95%CI 3.99 – 8.33, p < 0.001). Median PFS was 3.4 months for B group, 3.7 months for I group (HR vs B 1.35, 95% CI 1.03 – 1.77, p = 0.032) and 1.9 months for W group (HR vs B 2.51. 95% CI 1.80- 3.50, p < 0.001). Similar results were obtained stratifying the model by Institution. Conclusions: This clinical prognostic score, that was generated in patients treated with second-line chemotherapy, is able to highly predict outcomes of patients treated with IO. These results demonstrated that in pre-treated aNSCLC pts, the worst category has a dismal absolute life expectancy, and probably would not benefit from any active systemic therapy (independently if CHT or IO). Perhaps for these pts best supportive care could be the best choice.

scholarly journals FOLFIRI regimen: an effective second-line chemotherapy after failure of etoposide–platinum combination in patients with neuroendocrine carcinomas grade 3

2012 ◽  
Vol 19 (6) ◽  
pp. 751-757 ◽  
Author(s):  
O Hentic ◽  
P Hammel ◽  
A Couvelard ◽  
V Rebours ◽  
M Zappa ◽  
...  
Keyword(s):  
Serum Alkaline Phosphatase ◽  
Performance Status ◽  
Objective Response ◽  
Good Condition ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Second Line ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
Neuroendocrine Carcinomas

Patients with neuroendocrine carcinomas (NECs) grade 3 have a poor prognosis. Etoposide–platinum combination is the standard chemotherapy but the role of a second-line therapy remains unknown. Irinotecan alone or in combination has shown some efficacy in patients treated for small cell lung cancer which had pathological similarities with neuroendocine tumors. The aim of this study is to determine safety and efficacy of the FOLFIRI regimen in patients with NECs grade 3 after failure of etoposide–platinum combination. This study was retrospective, including patients with NECs grade 3 and treated with the FOLFIRI regimen after progression or toxicity of etoposide–platinum combination in first-line. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≥3 and/or serum alkaline phosphatase ≥5×upper limit of normal value (ULN) and/or bilirubin ≥1.5×ULN were excluded. Among 39 patients who failed etoposide–platinum combination, 19 (49%; 12 women, median age 53 (29–78) years) received the FOLFIRI regimen with a median number of 6 (1–16) courses. Six patients (31%) had at least one episode of grades 3–4 toxicity (neutropenia, n=3; diarrhea, n=3) without toxic death. Six patients (31%) had objective response, 6 (31%) stable disease, and 7 (38%) tumor progression. Median progression-free survival under FOLFIRI was 4 months. Overall survival was 18 vs 6.8 months in noneligible patients. FOLFIRI regimen is a safe and potentially efficient chemotherapy given as second-line in patients with NECs grade 3 who remain in good condition and with correct liver tests after failure of etoposide–platinum combination. These results should be confirmed in a future prospective study.

Tremelimumab in combination with durvalumab in first or second-line mesothelioma patients: Safety analysis from the phase II NIBIT-MESO-1 study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8558-8558 ◽  
Author(s):  
Luana Calabro ◽  
Aldo Morra ◽  
Diana Giannarelli ◽  
Giovanni Amato ◽  
Erica Bertocci ◽  
...  
Keyword(s):  
Phase Ii ◽  
Liver Toxicity ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Safety Analysis ◽  
Primary Objective ◽  
Second Line ◽  
Open Label ◽  
Ecog Performance Status

8558 Background: The anti-CTLA-4 tremelimumab at two different dose-schedules of administration showed promising activity in second-line malignant mesothelioma (MM) patients (Calabrò et al., Lancet Oncol, 2013; Calabrò et al., Lancet Respir Med, 2015). These initial results and the efficacy of targeting the PD-1/PD-L1 axis in different tumor types, prompted the NIBIT-MESO-1 study aimed at investigating the efficacy and safety of tremelimumab combined with the anti-PD-L1 durvalumab in mm patients. We report the safety analysis from the fully-enrolled NIBIT-MESO-1 study. Methods: The NIBIT-MESO-1 is a phase II, open-label, single Center study. Forty mm patients received tremelimumab at 1 mg/Kg i.v. every 4 weeks (Q4W) for 4 doses, and durvalumab at 20 mg/Kg i.v. Q4W for 13 doses. Primary objective is immune-related (ir)-objective response rate; secondary are safey, ir-disease control rate, ir-progression free survival, and overall survival. Tumor assessment per ir-modified RECIST or ir-RECIST 1.1 for pleural or peritoneal MM, respectively, was performed at baseline and q12 weeks. Adverse events (AEs) were recorded according to CTC v4.0. (ClinicalTrials.gov Id: NCT02588131). Results: From October 2015 to October 2016, 40 mm patients (38 pleural and 2 peritoneal), median age 64 years (range 41-80), ECOG performance status 0 (n = 19) or 1 (n = 21) were enrolled in the study. mm histology was epithelioid (n = 32), biphasic (n = 5), sarcomatoid (n = 2) or undefined (n = 1). As of January 2017, 12 first or 28 second-line mm patients received a median of 5.5 doses of therapy (range = 1-13). Twenty-four patients (60%) experienced any grade irAEs: 5 patients (12.5%) had grade 3-4 AEs, the most frequent being hepatotoxicity (7.5%). AEs were generally manageable and reversible per protocol guidelines. Three patients (7.5%) were discontinued due to treatment-related AEs (1 trombocytopenia, 1 limbic encephalitis, 1 liver toxicity). Conclusions: The combination of tremelimumab and durvalumab is safe and manageable in mm patients. Clinical trial information: NCT02588131.

Pegilodecakin as monotherapy or in combination with anti-PD-1 or tyrosine kinase inhibitor in heavily pretreated patients with advanced renal cell carcinoma (RCC): Updated results from phase I/Ib IVY study.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 679-679
Author(s):  
Aung Naing ◽  
Kyriakos P. Papadopoulos ◽  
Deborah J.L. Wong ◽  
Raid Aljumaily ◽  
Annie Hung ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Phase 1 ◽  
Performance Status ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Interleukin 10 ◽  
Median Number ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Heavily Pretreated

679 Background: Pegilodecakin (PEG), a pegylated recombinant human interleukin-10, has demonstrated clinical benefit and manageable toxicity in advanced RCC (Naing et al. 2016 JCO, Naing et al. 2019 Lancet Oncol). As part of the multi-arm (arm A to J) phase 1 IVY study, PEG alone (Part A) or in combination with pazopanib (Part G) or anti-PD-1 (pembrolizumab or nivolumab; Parts H+I) were investigated in heavily pretreated RCC patients (pts). Methods: In a phase 1/1b study which enrolled 353 pts in the US from 2013 to 2017, we analyzed treatment-related adverse events (TRAEs) graded by CTCAE v 4.02, tumor response by irRC, progression-free survival (PFS), and overall survival (OS) for all the advanced RCC pts who received PEG-containing treatment (n=66). Data cut-off was February 19, 2019. Results: Sixty six heavily pretreated RCC pts received PEG alone (n=24, 1-20 µg/kg), with pazopanib (n=4, 10µg/kg), with pembrolizumab (n=9, 10-20 µg/kg), or with nivolumab (n=29, 10-20 µg/kg). Most pts were male (70%), median age 62.5 years, initially diagnosed as stage IV (42%) with clear cell histology (64%), ECOG performance status of 1 (58%), and intermediate/poor (73%/14%) risk per IMDC category. Patients received a median number of 2 prior therapies. Most common grade 3/4 TRAEs were anemia (32%), thrombocytopenia (15%), and hypertriglyceridemia (14%). No pts died due to a TRAE. Median follow-up was 31.5 months. Conclusions: PEG alone or in combination with anti-PD-1 or pazopanib suggested some clinical activity with manageable toxicity in advanced RCC pts. These findings support further ongoing studies of PEG combinations in RCC pts. Clinical trial information: NCT02009449 .[Table: see text]

Statins (ASIs) may improve the outcome of erlotinib as second line treatment (tx) in patients (pts) with metastatic non-small cell lung cancer (mNSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18108-e18108
Author(s):  
Natalie Maimon ◽  
Daniel Keizman ◽  
Maya Gottfried
Keyword(s):  
Cox Model ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Female Gender ◽  
Partial Likelihood ◽  
Second Line ◽  
Ecog Performance Status ◽  
Group 2 ◽  
Group 1

e18108 Background: The EGFR inhibitor erlotinib is a standard second line tx for mNSCLC. Statins are used in the tx of hyperlipidemia. Pre-clinical and clinical studies in several cancer types have shown that they may inhibit tumor growth. Their effect on the outcome of erlotinib as second line tx in mNSCLC is poorly defined. We aimed to study the effect of statins on the outcome of erlotinib as second line tx for mNSCLC. Methods: We performed a retrospective study of an unselected cohort of pts with mNSCLC, who were treated continuously with 150mg of oral erlotinib. Pts were divided into 2 groups: (1) statins users and (2) statins naive. The effect of statins use on objective response, progression free survival (PFS) and overall survival (OS), was tested with adjustment of other known confounding risk factors using a chisquare test and partial likelihood test from cox model. Results: Between 2005-2011, 107 pts with mNSCLC were treated with second line erlotinib. There were 51 statins users (group 1) and 56 nonusers (group 2). All users started statins before erlotinib tx initiation. The groups were balanced regarding the following known clinical prognostic factors: female gender, ECOG performance status, active smoking, anemia, adenocarcinoma histology type, EGFR mutation (positive vs negative + unknown). Objective response in group 1 vs 2 was partial response (PR) 41% vs 29% (p=0.15), stable disease (SD) 41% vs 25% (p=0. 11), and progressive disease (PD) 18% vs 46% (OR=2.5, p=0.07). Median PFS was 12 vs 3 ms (HR 0.44 in statins users, p=0.02). Median OS was 35 vs 19 ms (HR 0.63, p=0.1). Conclusions: Statins may improve the outcome of pts with mNSCLC that are treated with erlotinib as second line tx. This should be investigated prospectively, and if validated, applied in clinical practice and clinical trials.

CheckMate 384: Phase IIIb/IV trial of nivolumab (nivo) 480 mg Q4W versus 240 mg Q2W after ≤ 12 months of nivo in previously treated advanced NSCLC.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 100-100 ◽  
Author(s):  
Edward B. Garon ◽  
Niels Reinmuth ◽  
Lionel Falchero ◽  
Yolanda Garcia Garcia ◽  
José Hureaux ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Performance Status ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Second Line ◽  
Efficacy And Safety ◽  
Open Label ◽  
Ecog Performance Status ◽  
Previously Treated

100 Background: Nivo is approved as 240 mg Q2W in the EU and Japan and 240 mg Q2W or 480 mg Q4W in the US and Canada for second-line treatment (tx) of advanced NSCLC. Pharmacokinetic modeling in various tumors predicts that exposure, efficacy and safety can be maintained with less frequent Q4W dosing, which may provide a more convenient tx option. We present an interim analysis of efficacy and safety from CheckMate 384 (NCT02713867), an international, open-label, randomized phase 3b/4 trial evaluating less frequent nivo dosing (480 mg Q4W vs 240 mg Q2W) in patients (pts) with advanced NSCLC and prior Q2W nivo tx. Methods: Pts (N = 329) with previously treated histologically confirmed stage IIIB/IV or recurrent NSCLC, ECOG performance status 0–2, and prior tx with nivo 3 mg/kg or 240 mg Q2W for ≤12 mo, with ≥2 consecutive assessments of complete / partial response or stable disease, were randomized 1:1 to nivo 480 mg Q4W or 240 mg Q2W over a 30-min infusion. Co-primary endpoints: post-randomization (RND) progression-free survival rates (PFS) at 6 mo and 1 y. Secondary endpoints included safety. Due to tx landscape changes in NSCLC, statistical analyses were amended for a reduced sample size. One-sided 95% CIs were generated to compare PFS rates; presented data analyses are descriptive. Results: Of 166 and 163 pts randomized to 480 mg Q4W and 240 mg Q2W, 164 and 161 pts were treated, respectively. Median follow-up was 9.5 mo (480 mg Q4W) and 10.2 mo (240 mg Q2W). Baseline characteristics were balanced between tx arms. Stratified PFS rates post-RND were comparable between tx arms at 6 mo and 1 y (Table). Safety profiles were similar; any grade tx-related adverse events (TRAEs) and TRAEs leading to discontinuation were reported in 48% vs 61% and 6% vs 9% of pts with 480 mg Q4W vs 240 mg Q2W. No tx-related deaths were reported. Conclusions: Nivo 480 mg Q4W showed similar efficacy and safety to 240 mg Q2W in pts with disease control on nivo, supporting the potential use of 480 mg Q4W as a more convenient dosing option for second-line NSCLC tx. Clinical trial information: NCT02713867. [Table: see text]

Safety and efficacy of pazopanib in heavily pretreated and treatment-naive patients with metastatic renal cell carcinoma (mRCC): A single center experience of the Medical University of Vienna, Austria.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15090-e15090 ◽  
Author(s):  
Manuela Schmidinger ◽  
Marija Bojic ◽  
Ursula Maria Vogl ◽  
Christoph Klingler ◽  
Gero Kramer ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Ecog Performance Status ◽  
University Of Vienna ◽  
Single Center Experience ◽  
Heavily Pretreated ◽  
Treatment Naïve ◽  
Pretreated Patients ◽  
Medical University

e15090 Background: Treatment with pazopanib was shown to improve objective response rates (ORR) and progression free survival (PFS) when compared to placebo in treatment-naïve or cytokine-pretreated patients with mRCC. We assessed the efficacy and safety of pazopanib in an unselected group of mRCC-patients at the Medical University of Vienna. Methods: Medical records of all patients who were treated with pazopanib between June 2010 and January 2012 were retrospectively reviewed. Pazopanib was prescribed at a dose of 800 mg daily. Treatment was given until disease progression or unacceptable toxicity. ORR was assessed by RECIST criteria. PFS and overall survival (OS) were calculated from the first day of pazopanib until progression and/or death, respectively. Results: Forty patients with a median age of 69 years (range 47-82) are currently evaluable for this analysis. The majority of patients (61%) presented with an ECOG Performance status of 0 and were classified as intermediate risk (55%) according to the MSKCC risk group classification. All patients had undergone nephrectomy and the majority (75%) had predominantly clear cell tumors. Most of the patients (66%) were diagnosed with three or more metastatic sites. Eighty percent of the patients were heavily pretreated, most commonly with three or more different types of targeted agents. Eight patients (20%) received pazopanib in first-line. Objective remission and disease stabilization were observed in 27% and 30% of the entire population. PFS and OS were 5 months (95%CI 3.07-6.86) and not reached, respectively. The most commonly observed all grade toxicities included fatigue (97%), anorexia (78%), hypertension (82%), diarrhoea (73%), nausea (62%) and vomiting (54%). The most common grade 3 or 4 toxicities were fatigue (68%), hypertension (47%) and diarrhoea (29%). Conclusions: Pazopanib appears effective in the setting of extensively pretreated patients. A later stage of the disease might have led to the unexpected higher incidence of off-target side effects such as fatigue and gastro-intestinal symptoms.

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