Treatment with bevacizumab in patients with metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14083-e14083
Author(s):  
Janja Ocvirk ◽  
Martina Rebersek ◽  
Marko Boc ◽  
Maja Ebert Motara ◽  
Tanja Mesti
Keyword(s):  
Clinical Practice ◽  
Adverse Events ◽  
Metastatic Disease ◽  
Performance Status ◽  
Progression Free Survival ◽  
Routine Clinical Practice ◽  
First Line ◽  
Ecog Performance Status ◽  
Good Tolerability ◽  
Previously Treated

e14083 Background: This study was designed to prospectively evaluate the safety and toxicity of bevacizumab in mCRC patients (pts) with mCRC pts in routine clinical practice as well as selection of pts. Methods: Baseline characteristics, pre-specified bevacizumab-related adverse events, and efficacy data were collected from 273 mCRC pts who started bevacizumab-containing therapy between January 2008 and August 2010. Results: The data from 273 pts (median age 62) were included in the evaluation. The ECOG performance status (PS) at baseline was 0 in 60%, 1 in 37% and 2 in 3% of pts. Eighty pts (29%) received adjuvant chemotherapy, and 84 (31%) received chemotherapy ± bevacizumab or cetuximab for prior treatment of metastatic disease. Majority of the 273 pts received irinotecan-based chemotherapy (65%). Complete response (CR) was reported in 7%, partial response (PR) in 31% and stable disease (SD) in 36% of the first-line treated pts. In pts previously treated for metastatic disease CR, PR and SD were 6%, 24% and 45%, respectively. In the first-line pts median progression-free survival (PFS) was 10.9 months (95% confidence interval [CI], 9.8 - 12.0), while median overall survival (OS) was 24.3 months (95% CI, 21.4 – 30.3). PFS was 10, 9 and 8.7 months and OS was 16.7, 13.5 and 12.8 months in pts previously treated for metastatic disease with chemotherapy, chemotherapy + cetuximab or chemotherapy + bevacizumab, respectively. Two-year survival rate was 51% in the first-line pts and 32%, 14% and 38% in pts previously treated for metastatic disease with chemotherapy, chemotherapy + cetuximab and chemotherapy + bevacizumab, respectively. Metastasectomy was performed in 39 (15.5%) of the pts. One hundred and nine pts received bevacizumab with subsequent chemotherapy and CR, PR and SD were 1%, 9% and 30%. Overall rates of bevacizumab-related grade 1-2/3-4 adverse events were: proteinuria 38/9 %, hypertension 16/3 %, thromboembolic events 1/5 %, infection 2/3 %, bleeding 2/1 % and fistula 0/1 %. Conclusions: The authors concluded that bevacizumab-containing therapy and use of bevacizumab for long period of time demonstrated efficacy and good tolerability when used as a first-, second- and third-line treatment in routine clinical practice.

Efficacy and tolerability of FOLFOX6 as first-line treatment for advanced gastric and esophagogastric junction cancers (AGC): A single-center experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14705-e14705
Author(s):  
Rozana Abdul Rahman ◽  
MinYuen Teo ◽  
Felicity McDonnell ◽  
Raymond S. McDermott
Keyword(s):  
Metastatic Disease ◽  
Performance Status ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Median Number ◽  
Published Data ◽  
Line Treatment ◽  
First Line ◽  
Ecog Performance Status ◽  
First Line Treatment

e14705 Background: There are a number of options for first line treatment for AGC. We sought to review the efficacy and tolerability of FOLFOX (F) in AGC, and compare outcomes with anthracycline-based (A) ctx-treated patients (pts). Methods: Pts with AGC treated with F and A (EOX and ECF) were identified from institutional database. Pt. demographics, disease characteristics and treatment details were extracted from medical charts and pharmacy database. Progression-free survival (PFS) and overall survival (OS) were calculated from commencement of ctx to radiographic evidence of progression and death, respectively, estimated with the Kaplan-Meier method. Comparisons were made via log-rank method. Other descriptive statistics calculated via t-test or chi-square methods as appropriate. Results: Between July 05 and December 11, 27 pts were treated with F. Twenty-one (77.8%) were male and median age was 68yrs (range: 42 – 77). ECOG performance status was 0 -1 in 24 pts (88.9%) and 2 in 3 (11.1%). Median Charlson score prior to metastatic disease was 2 (range: 0 – 3). Three had relapsed disease and another three had locally-advanced disease. Sites of metastatic disease were liver (12), peritoneum (12), non-regional nodes (2) and lungs (2). Median number of cycles of F was 5 (range: 1 - 12), 51.8% of pts completed ≥10 cycles, while the rest discontinued treatment due to disease progression (33%) and toxicities (14.8%). 21 pts (77.8%) required dose reduction and 17 (63%) experienced treatment delay. Fourteen (51.8%), 6 and 2 pts had 2nd, 3rd and 4th line of ctx, respectively. Median PFS was 7.2 mos and median OS is 9.7 mos. Sixteen pts were treated with A. Pts were significantly younger (p=0.002) but other characteristics were similar. Median PFS with A was 6.6 mos and median OS was 9.2 mos. The hazard ratio (F vs A) for PFS was 1.11 (95% CI 0.56 to 2.18, p = 0.77) and for OS was 0.73 (95% CI 0.36 to 1.51, p = 0.40). Conclusions: Despite an older pts cohort with co-morbidities, high percentage of treatment delays and dose reductions, our data suggest that significant percentage of pts were able to complete ≥10 cycles of F and subsequent therapies. Outcomes are comparable to our A cohort and published data.

Phase II trial of combined chemotherapy with irinotecan, S-1, and bevacizumab (IRIS/Bev) in patients with metastatic colorectal cancer (mCRC): Final analysis—Hokkaido Gastrointestinal Cancer Study Group (HGCSG) trial.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 460-460
Author(s):  
Satoshi Yuki ◽  
Yoshito Komatsu ◽  
Hiraku Fukushima ◽  
Takahide Sasaki ◽  
Toraji Amano ◽  
...  
Keyword(s):  
Adverse Events ◽  
Primary Endpoint ◽  
Performance Status ◽  
Rest Period ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
First Line Treatment

460 Background: The FIRIS study (Muro K et al. Lancet Oncol 2010;11:853–860) previously demonstrated the non-inferiority of Irinotecan plus S-1 (IRIS) to FOLFIRI for mCRC, with progression-free survival (PFS) as the primary endpoint. We previously reported that IRIS plus bevacizumab (IRIS/Bev) is very effective as first-line treatment (Komatsu Y et al. Acta Oncol. 2012 May 4). We now report the final results of this study. Methods: Eligible patients had to have mCRC with a confirmed diagnosis of adenocarcinoma, an age of >20 years, ECOG performance status (PS) of 0-1, and no history of prior chemotherapy. S-1 (40-60 mg depending on patients body surface area) was given orally, twice daily for 2 consecutive weeks, and 100 mg/m2irinotecan and 5 mg/kg bevacizumab was given intravenously on day 1 and 15, followed by 2-week rest period, within a 4-week cycle. The primary endpoint was safety. The secondary endpoints included overall response (OR), PFS, and overall survival (OS). Results: A total of 53 patients were enrolled from October 2007 through March 2009. The results were reported for 52 patients with evaluable lesions. The clinical characteristics of the patients were as follows. The median age was 63.5 years (range, 48 to 82). The male:female ratio was 3:2. The most common grade 3 or 4 adverse events were neutropenia (27%) and diarrhea (17%). Grade 3 or 4 hypertension (21%) was attributed to bevacizumab, but there were no life-threatening adverse events, such as gastrointestinal perforation. On an intention-to-treat basis, OR was 63.5% [95% confidence interval (CI) 50.4-76.5%], and the disease control rate was 94.2%. With a median follow-up time of 51.7 months, median PFS was 17.0 months (95%C.I. 14.2-19.8 months) and median survival time was 39.6 months (95%C.I. 34.2-45.0 months). Conclusions: IRIS/Bev is a remarkably active and generally well-tolerated first-line treatment for patients with mCRC. Randomized control trial comparing this regimen with oxaliplatin containing regimen(XELOX or mFOLFOX6 plus bevacizumab: TRICOLORE study) is already started. Clinical trial information: NCT00569790.

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]

The prognostic impact of bone metastasis in urothelial carcinoma treated with first-line platinum-based chemotherapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 415-415
Author(s):  
Husam Alqaisi ◽  
Zachary William Neil Veitch ◽  
Carlos Stecca ◽  
Jeenan Kaiser ◽  
Scott A. North ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Performance Status ◽  
Progression Free Survival ◽  
Response To Treatment ◽  
Prognostic Impact ◽  
First Line ◽  
Ecog Performance Status ◽  
Cancer Centre ◽  
Platinum Based Chemotherapy ◽  
Line Setting

415 Background: Metastatic urothelial carcinoma (mUC) is an aggressive disease with a median overall survival (OS) of ≈ 15 months. In the first-line setting, key prognostic factors include ECOG performance status, white blood cell count, and response to treatment per the Galsky nomogram. Bone metastases (BM) in mUC are associated with morbidity and mortality but are grouped with visceral disease; hence, their impact on prognosis is not well established. We aimed to assess the survival impact of BM in mUC patients treated with first-line platinum-based chemotherapy (PBC). Methods: A retrospective collection of patient and tumor characteristics, with clinical response to treatment (complete response [CR], partial response [PR]; stable disease [SD] or progressive disease [PD]) for patients treated at Princess Margaret Cancer Centre, Tom Baker Cancer Centre, and Cross Cancer Institute from 2005-2018 was performed. Progression-free survival (PFS) and OS were estimated using the Kaplan-Meier method. Univariate (UVA) followed by multivariate analysis (MVA) of patient variables [Cox] using PFS and OS was performed. Results: Overall 376 mUC patients were included; 222 (59%) had soft-tissue metastases (STM) only, 70 (19%) had bone-only metastases, and 84 (22%) had both STM and BM. Overall, 35% had PR or CR, 19% had SD, and 39% had PD (7%: unknown response). The median PFS and OS for the whole cohort were 5.6 months (95%CI: 4.8-6.4) and 9.7 months (95% CI: 8.8-10.8) respectively. Select UVA by metastatic site showed inferior PFS for bone-only (p=0.03) and combination STM and BM (p=0.017). Only combination STM and BM were significant on UVA for OS (p=0.002). MVA showed that bone-only metastases (p=0.03) and ECOG 3-4 (p<0.0001) were associated with worse PFS (Table). Predictors of worse OS were the combination of STM and BM (p=0.02), ECOG 3-4 (p=0.001), and WBCs ≥ULN (p=0.02), (Table). Conclusions: BM are a significant predictor of worse outcomes for mUC patients treated with first-line PBC. Consideration as a treatment stratification factor for future studies is suggested. Strategies for the treatment of mUC patients with BM (ie: bone targeted agents) in the first-line setting should be addressed in future trials. [Table: see text]

Update results from ALTER-C-001: Efficacy and safety of anlotinib plus XELOX regimen as first-line treatment followed by maintenance monotherapy of anlotinib for patients with mCRC-A single-arm, multicenter, phase Ⅱ clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15550-e15550
Author(s):  
Jin Yan ◽  
Yunwei Han ◽  
Li Zhang ◽  
Yongdong Jin ◽  
Hao Sun
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Performance Status ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Open Label ◽  
Ecog Performance Status ◽  
Multicenter Phase ◽  
First Line Treatment

e15550 Background: The combination of anti-VEGF or anti-EGFR targeted drugs with chemotherapy is the standard first-line therapy for metastatic colorectal cancer (mCRC), and the followed maintenance treatment is an optional approach to balance the efficacy and toxicity. However, studies regarding the maintenance strategies based on antiangiogenic TKIs are limited currently. Anlotinib, a novel oral multi-target TKI which can inhibit both tumor angiogenesis and tumor cell proliferation simultaneously, substantially prolonged the PFS with manageable toxicity for refractory mCRC in the phase III ALTER0703 clinical trial. Here we report an update on the effectiveness and safety of anlotinib plus XELOX as first-line treatment followed by anlotinib monotherapy for mCRC. Methods: In this open label, single-arm, multicenter phase II clinical trial, 53 mCRC patients without prior systemic treated, aged 18-75 and an ECOG performance status of 0 or 1 were planned to recruit. Eligible patients received capecitabine (1000 mg/m2, po, d1-14, q3w) and oxaliplatin (130 mg/m2, iv, d1, q3w) plus anlotinib (10mg, po, d1̃14, q3w) treatment for 6 cycles. After 6 cycles of inducing therapy, patients would receive anlotinib (12mg, po, d1̃14, q3w) as maintenance therapy until disease progression or intolerable adverse events (AEs). The primary endpoint was PFS; Secondary endpoints included ORR, DCR, DOR and safety. Results: By the data analysis cutoff date of January 22, 2021, a total of 18 patients were enrolled, of which 12 patients were available for efficacy assessment. In best overall response assessment, there were 50.0% PR (6/12), 33.3% SD (4/12) and 16.7% PD (2/12). The ORR was 50.0% (95% CI, 21.1-78.9%) and DCR was 83.3% (95% CI, 51.5-97.9%). The longest duration of treatment was 8.8 months and the response was still ongoing. The median PFS was not reached. The most common treatment related adverse events (TRAEs) of any grade (≥20%) were leukopenia, hypertension, neutropenia, diarrhea, fatigue, hypertriglyceridemia. Grade 3/4 TRAEs included hypertension (22.2%), hypertriglyceridemia (11.1%), lipase elevated (11.1%) and neutropenia (5.6%). No grade 5 AEs occurred. Conclusions: The update results suggested that anlotinib combined with XELOX as first line regimen followed by anlotinib monotherapy showed promising anti-tumor activity and manageable safety for patients with mCRC. And the conclusions needed to be confirmed in trials continued subsequently. Clinical trial information: ChiCTR1900028417.

A phase II study of S-1 for previously treated small cell lung cancer (SCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19074-e19074
Author(s):  
K. Kudo ◽  
F. Ohyanagi ◽  
A. Horiike ◽  
E. Miyauchi ◽  
I. Motokawa ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Median Number ◽  
Ecog Performance Status ◽  
Treatment Regimens ◽  
Platinum Based Chemotherapy ◽  
Previously Treated

e19074 Background: S-1 is a novel oral 5-fluorouracil derivative that exhibits obvious activity against various tumor types including NSCLC. However, the effects of S-1 against SCLC have not been reported. The present phase II trial assesses the efficacy and safety of S-1 in previously treated SCLC patients. Methods: Eligible patients had pathologically documented SCLC that relapsed after platinum-based chemotherapy, ECOG performance status (PS) 0–2, and adequate bone marrow, kidney and liver function. Patients with untreated or symptomatic brain metastasis were excluded. Treatment comprised the oral administration of S-1 at 40 mg/m2 twice each day for 28 days every 6 weeks. The primary end point was the objective tumor response rate (RECIST). Secondary endpoints included progression-free survival and overall survival. Results: Twenty-six evaluable patients were enrolled (Simon's two-stage optimal design; α = 0.1; β = 0.1; P0 = 0.05; P1 = 0.25) with the following characteristics: male: female, 22/4; median age, 68 (33 - 79) y; PS0–1, n = 21; PS2, n = 5. The median number of prior treatment regimens was 2 (1–3). S-1 was administered for a mean of 1.3 cycles (1 - 5). One patient (3.8%) partially responded, 10 (38.5%) had stable and 15 (57.7%) had progressive disease. The overall response rate was 3.8% and the disease control rate was 42.3%. The median time to progression was 33 days. The median survival time was 8.0 months and the 1-year survival rate was 23%. This regimen was well tolerated. The common grade 3/4 toxicities included neutropenia (7.7%), leukopenia (7.7%), anemia (7.7%), hyponatremia (7.7%), rush (7.7%), infection (7.7%), and diarrhea (3.8%). None of the patients developed febrile neutropenia and no deaths were attributed to treatment. Conclusions: S-1 is well tolerated but has low activity as a single agent in previously treated patients with SCLC. No significant financial relationships to disclose.

Bevacizumab in combination with first-line metastatic chemotherapy in patients with advanced nonsquamous non-small cell lung cancer (NSCLC): Results from the cohort study EOLE.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18005-e18005
Author(s):  
Christos Chouaid ◽  
Roland Schott ◽  
Lionel Falchero ◽  
Franck Bonnetain ◽  
Julien Neaume ◽  
...  
Keyword(s):  
Cohort Study ◽  
Performance Status ◽  
Locally Advanced ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Large Cell Carcinoma ◽  
First Line ◽  
Ecog Performance Status ◽  
Study Results ◽  
Chi2 Test

e18005 Background: EOLE, a large cohort of 423 patients included in 1 year (July 2010 – July 2010) with locally advanced, metastatic or recurrent non-squamous NSCLC, aimed to describe the targeted population receiving first-line bevacizumab (Bev) in addition to chemotherapy with regards to progression-free survival, overall survival, safety and quality of life in real clinical practice. Methods: Patients who received physician’s choice of 1st-line Bev-containing treatment were included in this cohort study. Results: This analysis describes the inclusion data of 417 patients consisting of adenocarcinoma (92%), large cell carcinoma (4%), undifferentiated carcinoma in predominantly non-squamous (3%), bronchoalveolar carcinoma (1%). Patient characteristics were as follow: the median age being 60 (years) [32; 84], more males than females (68%), 40% had a baseline ECOG Performance Status (PS) 0, 47% of PS 1 and 12% of PS 2, most patients had Stage IV disease (91%), 13% of patients had never smoked. Tumor location was reported as central for 17% of patents and among them 4% was in contact with the large vessels. For 3% of the lesions a cavitation was notified; and 20% of included patients had brain metastases. The main comorbidities at the inclusion were: cardiovascular (45%), arterial thromboembolic and /or venous (20%) with pulmonary embolism (3%); related to the tumor lesion - bloody sputum (4%) and hemoptysis (1%). 68% of patients have received the dose of Bev 7.5mg/kg q3w; for 49% of patients Bev was combined with cisplatin/pemetrexed, 24% with carboplatin/paclitaxel, 13% with carboplatin/pemetrexed and 7% with cisplatin/gemcitabine. The EGFR mutation analysis was carried out for about 50% of patients. Conclusions: Compared to AVAil and SAil studies, EOLE cohort included more patients classified as having: a baseline PS of 2 (p <0.0001, Fisher test), a never smoked status (p<0.0001, chi2 test) and an adenocarcinoma (92%) (p<0.0001, chi2 test). Around a half of included patients received combination Bev - cisplatin /pemetrexed.

Retrospective analysis of sorafenib as first or second target therapy in mRCC patients in Italian centers: An update.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15524-e15524
Author(s):  
Lisa Derosa ◽  
Angela Gernone ◽  
Franco Morelli ◽  
Teodoro Sava ◽  
Fable Zustovich ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Retrospective Analysis ◽  
Target Therapy ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Daily Clinical Practice ◽  
Duration Of Treatment ◽  
Ecog Performance Status

e15524 Background: With several agents available for the treatment of metastatic renal cell carcinoma (mRCC) a better understanding of their use in daily clinical practice is fundamental in the decision-making process. Methods: The REtrospective analysis of Sorafenib (So) as 1st or 2nd targET therapy (RESET) in mRCC was a retrospective, observational field study that assessed the use and safety of So in clinical practice in Italian centers. Treatments were determined by physicians per local prescribing guidelines. Patients (pts) treated with So single agent as 1st or 2nd target therapy (TT) for mRCC between 1st Jan 2008 and 31st Dec 2010 were eligible for inclusion. Endpoints included safety, overall survival (OS), progression-free survival, response rate and treatment duration. Subgroup analyses included age, ECOG performance status, prior therapy, number of metastases and line of TT with So. Results: From Feb to Jul 2012, 358 pts from 37 Italian centers were enrolled. The most common ≥ grade 3 drug-related adverse events were hand-foot skin reaction (6.7%), rash (2.2%), hypertension, fatigue and diarrhea (1.7% each). In the overall population, median OS was 17.2 months (mos) (95% CI 15.4 – 19.6 mos) and median PFS was 5.9 mos (95% CI 4.9-6.7 mos). Median duration of treatment with So was 5.03 mos. Disease control (complete response + partial response + stable disease) was observed in 198(56%) pts. In pts receiving So as first or as second TT median OS was 19.9 mos (95% CI 15.9-25.3 mos) and 16.3 mos (95% CI 13.0-18.2 mos) respectively. In the subgroup of pts treated with So 1st TT followed by sunitinib (Su) 2nd TT (44 pts) and Su 1st TT followed by So 2nd TT (173 pts), median OS was 30.4 mos (95% CI 22.0-34.8 mos) and 16.6 mos (95% CI 13.1-18.2 mos) respectively. There were 269(76%) pts that received a total of 2 lines of therapy for mRCC, 133(38%) pts 3 lines and 43(12%) pts 4 lines of therapy. Conclusions: The efficacy and safety profile of So in the setting of Italian community-based daily clinical practice was similar to data reported in prospective clinical trials. The efficacy of So was observed in both the subgroups of pts receiving So as either the first or second TT for mRCC, with intriguing OS data in first line.

KEYNOTE-224: Phase II study of pembrolizumab in patients with previously treated advanced hepatocellular carcinoma.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS504-TPS504 ◽  
Author(s):  
Andrew X. Zhu ◽  
Jennifer J. Knox ◽  
Masatoshi Kudo ◽  
Stephen L. Chan ◽  
Richard S. Finn ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Disease Progression ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Locoregional Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Ecog Performance Status ◽  
Previously Treated

TPS504 Background: The tyrosine kinase inhibitor sorafenib is the standard of care for first-line hepatocellular carcinoma (HCC). For patients with HCC after disease progression on sorafenib or for those with intolerance to sorafenib, no approved therapies are available. Because HCC is often driven by inflammation and is also associated with a suppressed immunoenvironment, there is a strong rationale to evaluate immunotherapy in patients with this type of cancer. The single-arm, multisite, phase 2 KEYNOTE-224 study (ClinicalTrials.gov, NCT02702414) was designed to evaluate the efficacy and safety of the anti–PD-1 antibody pembrolizumab in patients with previously treated advanced HCC. Methods: Approximately 100 patients will be enrolled. Inclusion criteria include age ≥18 years, histologically or cytologically confirmed diagnosis of HCC Barcelona Clinic Liver Cancer (BCLC) stage C disease or BCLC stage B disease not amenable to or refractory to locoregional therapy, and disease not amenable to a curative treatment approach (eg, transplantation, surgery, or ablation). Patients must also have measurable disease based on RECIST v1.1 as confirmed by central imaging vendor review, documented objective radiographic progression after stopping treatment with sorafenib or intolerance to sorafenib, Child-Pugh liver score A, ECOG performance status 0-1, and predicted life expectancy > 3 months. Patients will be allocated to receive pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles (~2 years) or until disease progression, unacceptable toxicity, patient withdrawal of consent, or investigator decision. Response will be assessed every 9 weeks per RECIST v1.1 by central imaging vendor review. Adverse events (AEs) will be assessed throughout treatment and for 30 days thereafter (90 days for serious AEs) and graded per NCI CTCAE v4.0. The primary end point is objective response rate per RECIST v1.1 by central imaging vendor review. Secondary end points are overall survival; safety and tolerability; and duration of response, disease control rate, time to progression, and progression-free survival per RECIST v1.1 by central imaging vendor review. Enrollment in KEYNOTE-224 is ongoing. Clinical trial information: NCT02702414.

Final results of PEANUT: Pembrolizumab and nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as salvage therapy for metastatic urothelial carcinoma (UC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5017-5017
Author(s):  
Patrizia Giannatempo ◽  
Giuseppina Calareso ◽  
Marco Bandini ◽  
Laura Marandino ◽  
Daniele Raggi ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Open Label ◽  
Ecog Performance Status ◽  
Repair Gene ◽  
Good Tolerability ◽  
Blood Samples ◽  
Disease Response

5017 Background: Pembrolizumab (pembro) is a new standard of care in chemotherapy (CT) pre-treated patients (pts) with metastatic UC. Nab-paclitaxel demonstrated preliminary activity in advanced UC. In the PEANUT study (NCT03464734) we investigated their combination in advanced UC after CT failure. Methods: In an open-label, single-arm, phase 2 trial, pts received 200 mg pembro, intravenously (IV), on D1 and 125 mg/m2 IV nab-paclitaxel on D1 and D8, every 3 weeks, until disease progression (PD) or unacceptable toxicity. Inclusion criteria were: predominant UC histology, failure of ≤2 platinum-based CT for metastatic disease. Response was evaluated by RECIST v.1.1 criteria every 2 cycles. Biomarkers included PD-L1 combined positive score (CPS) and comprehensive genomic profiling on tumor and blood samples (FoundationONE and FoundationACT assay). The primary endpoint was the progression-free survival (PFS). The target was to detect an improvement in the median PFS from ≤3.0 months (H0) to ≥5.0 months (H1). Results: Between 01 and 12/2019, PEANUT study enrolled 65 pts: 24% were female, median age was 69 yrs (IQR: 61-73); 25% had failed > 1 prior systemic therapies; 35% had ECOG-performance status 1; 33% had liver metastases. The median TMB was 6.9 mut/Mb. After median follow-up (FUP) of 5.5 months, 34 pts have relapsed (52.3%). The median PFS was 5 months (95%CI: 3-not reached). The 3-month PFS was 60.7% (95%CI: 49.8-74.1). The confirmed objective response-rate (ORR) was 47.7% (95%CI: 35.2-60.4): 22 partial responses and 9 complete responses (13.8%). The median duration of response was not reached, and 4 pts (6.1%) are long-term responders ( > 12 months). Grade 3 treatment-related adverse events (TRAE) were seen in 20 pts (30.7%). Most common any-grade TRAE included alopecia (76%), neutropenia (33.3%) and asthenia (33%). Neither TMB nor CPS were significantly associated with PFS on univariable analyses. In matched tumor/blood samples, objective responses were seen in 8/10 pts with PI3KCA mutations (80%); 6/10 pts with RB1 alterations (60%); 5/12 pts with DNA damage repair gene alterations (41.7%). Conclusions: Pembro-nab-paclitaxel, the first salvage CT-immunotherapy combination in UC, demonstrated a good tolerability, promising PFS and a clinically meaningful ORR in II-III line setting of advanced UC. As more mature data on biomarker selection emerges, this combination warrants additional studies in either second-line or earlier disease settings. Clinical trial information: NCT03464734 .

Sign in / Sign up

Export Citation Format

Share Document