scholarly journals Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study

2021 ◽  
pp. JCO.21.00217
Author(s):  
Yoon-Koo Kang ◽  
Suzanne George ◽  
Robin L. Jones ◽  
Piotr Rutkowski ◽  
Lin Shen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Disease Control ◽  
Survival Data ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase Iii ◽  
Once Daily ◽  
End Point ◽  
Significant Difference ◽  
Phase Iii Study

PURPOSE Primary or secondary mutations in KIT or platelet-derived growth factor receptor alpha ( PDGFRA) underlie tyrosine kinase inhibitor resistance in most GI stromal tumors (GISTs). Avapritinib selectively and potently inhibits KIT- and PDGFRA-mutant kinases. In the phase I NAVIGATOR study ( NCT02508532 ), avapritinib showed clinical activity against PDGFRA D842V–mutant and later-line KIT-mutant GIST. VOYAGER ( NCT03465722 ), a phase III study, evaluated efficacy and safety of avapritinib versus regorafenib as third-line or later treatment in patients with unresectable or metastatic GIST. PATIENTS AND METHODS VOYAGER randomly assigned patients 1:1 to avapritinib 300 mg once daily (4 weeks continuously) or regorafenib 160 mg once daily (3 weeks on and 1 week off). Primary end point was progression-free survival (PFS) by central radiology per RECIST version 1.1 modified for GIST. Secondary end points included objective response rate, overall survival, safety, disease control rate, and duration of response. Regorafenib to avapritinib crossover was permitted upon centrally confirmed disease progression. RESULTS Four hundred seventy-six patients were randomly assigned (avapritinib, n = 240; regorafenib, n = 236). Median PFS was not statistically different between avapritinib and regorafenib (hazard ratio, 1.25; 95% CI, 0.99 to 1.57; 4.2 v 5.6 months; P = .055). Overall survival data were immature at cutoff. Objective response rates were 17.1% and 7.2%, with durations of responses of 7.6 and 9.4 months for avapritinib and regorafenib; disease control rates were 41.7% (95% CI, 35.4 to 48.2) and 46.2% (95% CI, 39.7 to 52.8). Treatment-related adverse events (any grade, grade ≥ 3) were similar for avapritinib (92.5% and 55.2%) and regorafenib (96.2% and 57.7%). CONCLUSION Primary end point was not met. There was no significant difference in median PFS between avapritinib and regorafenib in patients with molecularly unselected, late-line GIST.

S-1/docetaxel compared with the other standard S-1 based regimens as a first-line chemotherapy for patients with advanced gastric cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15173-e15173
Author(s):  
Tetsuya Kusumoto ◽  
Koji Ando ◽  
Satoshi Ida ◽  
Yasue Kimura ◽  
Hiroshi Saeki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Advanced Gastric Cancer ◽  
Survival Data ◽  
Objective Response ◽  
The Other ◽  
Phase Iii ◽  
First Line ◽  
Significant Difference ◽  
Line Chemotherapy

e15173 Background: S-1 monotherapy or S-1/CDDP have remained important as a standard chemotherapy regimen for patients with advanced gastric cancer (AGC), based on the randomized phase III trials. Although S-1/docetaxel has been reported highly active and well tolerated for AGC by many researchers, it could not show the superiority compared with S-1 monotherapy in the recent international randomized trial. We have also demonstrated that it might be effective for patients with Stage III AGC in both preoperative and postoperative adjuvant setting. The aim of this study was to evaluate efficacy, toxicity and validity of S-1/docetaxel retrospectively, compared with the standard regimens. Methods: We conducted a retrospective review of the data of 89 patients with AGC who received chemotherapy who were given S-1-containing regimens as the first line chemotherapy; 15 patients treated with S-1 monotherapy, 21 with S-1/CDDP, and 53 with S-1/docetaxel. The objective response, adverse event (AE), progression-free survival (PFS), and overall survival (OS) were compared between the three groups. Results: The overall response rates (ORRs) were obtained 6.7%, 38.1% and 30.2% for S-1 monotherapy, S-1/CDDP, and S-1/docetaxel, respectively. The incidence of AEs was more frequent in S-1 based combined treatments than in the S-1 monotherapy, however there was no significant difference in the severe AEs between each group. Survival data showed that the PFSs were 121 days, 199 days and 178 days, respectively, and there was the significant difference between S-1 monotherapy and S-1/docetaxel (p<0.05). The overall survival showed that the MSTs were not significantly different. The conversion rate to the subsequent treatments following S-1 monotherapy was higher than the other treatments. Conclusions: S-1/docetaxel was active and well tolerated for the patients with ARGC as the first line. Although the Japanese guideline for treatment of gastric cancer recommends S-1 monotherapy or S-1/CDDP as the standard regimens, docetaxel could be applied for patients with AGC in case of CDDP-resistant or –naïve patients.

Use of EGF A61G polymorphism to predict overall survival in a phase III study of gemcitabine plus cetuximab versus gemcitabine in patients with locally advanced or metastatic pancreatic adenocarcinoma (SWOG 0205).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 203-203
Author(s):  
Melissa Janae Labonte ◽  
Bryan H. Goldman ◽  
Wu Zhang ◽  
C. D. Blanke ◽  
Philip Agop Philip ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pancreatic Adenocarcinoma ◽  
Objective Response ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Entire Study ◽  
Egfr Signaling Pathway ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Phase Iii Study

203 Background: The SWOG 0205 phase III study failed to demonstrate an advantage from the addition of cetuximab to gemcitabine for overall survival (OS), progression-free survival (PFS) or objective response in advanced pancreatic cancer. Molecular markers may identify subgroups of pts who benefit from this regimen. This report summarizes the results of a pilot project aimed at screening germline single nucleotide polymorphisms (SNPs) in genes involved in gemcitabine metabolism pathway (CDA and RRM1) and EGFR signaling pathway (EGF, EGFR, IGF1, FCGR2A/3A, KRAS, IL8, COX-2, CCND1) to identify pts that may benefit from this treatment. Methods: Genomic DNA was extracted from 88 available serum samples for this molecular correlates pilot study. Sixteen SNPs were evaluated using PCR-based protocols. There were no differences in baseline characteristics or outcome between pts included in the analysis and the entire study population. Associations between genotype and OS were assessed using stratified Cox regression, with adjustment for treatment arm. Genotypes were parameterized as the number of dominant alleles. No p value adjustments were made for multiple comparisons. Results: Median age was 63.3 years (range: 29.6-85.0), and median OS (95% CI) was 5.7 months (mos) (range: 4.4-6.8) in this subset. There was a statistically significant association between EGF A61G SNP (rs4444903) genotype and OS (p=0.04). Among pts carrying the AA genotype, median OS was 8.4 mos (95% CI 4.9-15.0), as compared to 5.6 mos (95% CI 3.0-9.0) among those with the AG genotype and 5.3 mos. (95% CI 2.2-7.1) for the GG genotype. Evidence was weak for interaction between treatment arm and rs4444903 genotype (p=0.13). No significant associations between other SNPs and OS were observed. Conclusions: This exploratory study suggests that the EGF A61G polymorphism may be a useful molecular marker for predicting clinical outcomes in metastatic pancreatic adenocarcinoma pts treated with gemcitabine-based chemotherapy.

Randomized Phase III Evaluation of Cisplatin Plus Fluorouracil Versus Cisplatin Plus Paclitaxel in Advanced Head and Neck Cancer (E1395): An Intergroup Trial of the Eastern Cooperative Oncology Group

2005 ◽  
Vol 23 (15) ◽  
pp. 3562-3567 ◽  
Author(s):  
Michael K. Gibson ◽  
Yi Li ◽  
Barbara Murphy ◽  
Maha H.A. Hussain ◽  
Ronald C. DeConti ◽  
...  
Keyword(s):  
Overall Survival ◽  
Head And Neck ◽  
Response Rate ◽  
Cell Cancer ◽  
Objective Response ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Complete Response ◽  
Phase Iii ◽  
Significant Difference

Purpose To determine the response rate, survival and toxicity of infusional cisplatin plus fluorouracil (CF) versus cisplatin plus paclitaxel (CP) in patients with incurable squamous cell cancer of the head and neck, with the hypothesis that CP is superior. Patients and Methods Two hundred eighteen patients with locally advanced, recurrent, or metastatic disease were randomly assigned to CF (cisplatin 100 mg/m2 day 1 and fluorouracil 1,000 mg/m2/24 hours by continuous intravenous infusion day 1 through 4) or CP (cisplatin 75 mg/m2 day 1 and paclitaxel 175 mg/m2 over 3 hours on day 1). Cycles were repeated every 3 weeks until progression or a minimum of 6 cycles with complete response or stable disease. The primary outcome was overall survival. Secondary outcomes included response rate and toxicity. Results No significant difference in overall survival or response rate was seen. Estimated median survival was 8.7 months in the CF group and 8.1 month in the CP group. Objective response rate (complete response plus partial response) was 27% in the CF group and 26% in the CP group. Toxicity was similar between groups, with the most frequent including myelosuppression, thrombocytopenia, anemia, nausea, vomiting, and stomatitis. A total of 12 deaths occurred (CF, seven; CP, five) during treatment; eight from infection, two from hemorrhage, one from cardiac causes and one from unknown causes. Gastrointestinal and hematologic toxicities were more common in the CF group, whereas neurotoxicity was equivalent between groups. Conclusion This phase III, randomized, multicenter trial showed no difference in survival between patients treated with CF or CP.

scholarly journals Gemcitabine Plus Cisplatin Versus Fluorouracil Plus Cisplatin as First-Line Therapy for Recurrent or Metastatic Nasopharyngeal Carcinoma: Final Overall Survival Analysis of GEM20110714 Phase III Study

2021 ◽  
pp. JCO.21.00396
Author(s):  
Shaodong Hong ◽  
Yaxiong Zhang ◽  
Gengsheng Yu ◽  
Peijian Peng ◽  
Jiewen Peng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Nasopharyngeal Carcinoma ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Once Daily ◽  
Free Survival ◽  
End Point ◽  
Metastatic Nasopharyngeal Carcinoma ◽  
Phase Iii Study

PURPOSE GEM20110714 (ClinicalTrials.gov identifier: NCT01528618 ), the first randomized, phase III study of systemic chemotherapy in recurrent or metastatic nasopharyngeal carcinoma (NPC), reported significant progression-free survival improvement with gemcitabine plus cisplatin (GP) versus fluorouracil plus cisplatin (FP; hazard ratio, 0.55; 95% CI, 0.44 to 0.68; P < .001). Data from the final analysis of overall survival (OS) are presented here. METHODS From February 2012 to October 2015, 362 patients were randomly assigned to receive either GP (gemcitabine 1 g/m2 once daily on days 1 and 8 and cisplatin 80 mg/m2 once daily on day 1; n = 181) or FP (fluorouracil 4 g/m2 in continuous intravenous infusion over 96 hours and cisplatin 80 mg/m2 once daily on day 1; n = 181) once every 21 days. The primary end point was progression-free survival, which has been previously reported; OS was a secondary end point. RESULTS After a median follow-up time of 69.5 months with GP and 69.7 months with FP, 148 (81.8%) and 166 (91.7%) deaths occurred in the GP and FP arms, respectively. The estimated hazard ratio for OS was 0.72 (95% CI, 0.58 to 0.90; two-sided P = .004). The median OS was 22.1 months (95% CI, 19.2 to 25.0 months) with GP versus 18.6 months (95% CI, 15.4 to 21.7 months) with FP. The OS probabilities at 1, 3, and 5 years were 79.9% versus 71.8%, 31.0% versus 20.4%, and 19.2% versus 7.8%, respectively. Poststudy therapy was administered in 51.9% and 55.2% of patients in the GP and FP arms, respectively. CONCLUSION Among patients with previously untreated advanced nasopharyngeal carcinoma, those who receive GP have longer OS than those receive FP. Gemcitabine plus cisplatin should be considered a preferred front-line option for these patients.

A phase II trial of ZD6474 plus docetaxel in patients with previously treated NSCLC: Follow-up results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7016-7016 ◽  
Author(s):  
J. V. Heymach ◽  
B. E. Johnson ◽  
D. Prager ◽  
E. Csada ◽  
J. Roubec ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Survival Data ◽  
Locally Advanced ◽  
Primary Objective ◽  
Phase Iii ◽  
Double Blind Study ◽  
Once Daily ◽  
Platinum Based Chemotherapy

7016 Background: ZD6474, a once-daily oral agent, targets key signaling pathways in cancer by inhibiting VEGF, EGF and RET receptor tyrosine kinases. ZD6474 in combination with docetaxel (Doc) was assessed in patients (pts) with refractory non-small-cell lung cancer (NSCLC). Methods: Pts eligible for this randomized, double-blind study had locally advanced or metastatic (stage IIIB/IV) NSCLC after failure of 1st-line platinum-based chemotherapy. The primary objective was to determine whether once-daily oral ZD6474 (100 or 300 mg) + Doc (75 mg/m2 i.v. infusion every 21 days) prolonged progression-free survival (PFS) vs Doc alone (80% power to detect 50% prolongation at P<0.2). Overall survival was a secondary objective. Results: A total of 127 pts (73 male/54 female; median age 59 yrs, range 29–82) received ZD6474 100 mg + Doc (n=42), ZD6474 300 mg + Doc (n=44) or Doc (n=41). The study met its primary objective of PFS prolongation with the addition of ZD6474: median PFS was 19 wks for ZD6474 100 mg + Doc (HR=0.64; P=0.074); 17 wks for ZD6474 300 mg + Doc (HR=0.83; P=0.461); and 12 wks for Doc. A total of 64 pts (50%) presented with histology other than adenocarcinoma, including 37 with squamous, and 13 pts (10%) entered with CNS metastases. Exploratory subgroup analyses suggest advantages in PFS for ZD6474 + Doc vs Doc both for adenocarcinoma and for other lung cancer histologies. Common adverse events (AEs) included diarrhea, rash and asymptomatic QTc prolongation, all responded to standard management or dose interruption/reduction. Four pts with squamous experienced hemoptysis (ZD6474 100 mg + Doc, n=2 CTC grade 1/2; Doc, n=2 CTC grade 3/4). No fatal episodes of hemoptysis or any CNS hemorrhage AEs were reported in pts receiving ZD6474. Overall survival data were immature at the time of PFS analysis, and a mature survival analysis will be conducted at ∼75% of deaths (anticipated April 2006, and will be presented at the meeting). As of December 2005, 40/127 (31%) pts were alive, 5 of whom continue to receive ZD6474. The minimum follow-up of pts still alive was 17 months. Conclusions: ZD6474 + Doc prolonged PFS vs Doc alone, and these promising data have led to the initiation of Phase III evaluation of ZD6474 + Doc in 2nd-line NSCLC. [Table: see text]

Irinotecan versus best supportive care (BSC) as second-line therapy in gastric cancer: A randomized phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4540-4540 ◽  
Author(s):  
P. C. Thuss-Patience ◽  
A. Kretzschmar ◽  
T. Deist ◽  
A. Hinke ◽  
D. Bichev ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Locally Advanced ◽  
Phase Iii ◽  
Open Label ◽  
Logrank Test ◽  
Line Therapy ◽  
Phase Iii Study ◽  
Ecog Ps ◽  
Line Chemotherapy

4540 Background: Up to now the value of 2nd-line therapy for metastatic gastric cancer is unclear. So far there are no randomized phase III data comparing 2nd-line chemotherapy to BSC. Irinotecan has proven activity in 1st-line therapy. In this randomized phase III study we compared irinotecan to BSC to evaluate the value of 2nd- line chemotherapy for gastric cancer. Methods: Prospective multicenter randomized phase III study, open label. Eligibility: Metastatic or locally advanced gastro-esophageal junction or gastric adenocarcinoma. Objective tumor progession (PD) within 6 months after 1st- line chemotherapy. ECOG PS 0–2. Statistics: Primary endpoint: Overall survival (OS). Hypothesis: H1: OS(Irinotecan)>OS(BSC). Calculated number of pts needed (power 80%, alpha error 5%): 60 pts per arm. Stratification for a) PD less versus (vs) more than 3 months after 1st line chemotherapy, b) ECOG PS 0/1 vs 2. Treatment: Arm A: Irinotecan 250mg/m2 q3w (1st cycle) to be increased to 350 mg/m2, depending on toxicity. Arm B: BSC Results: Between Oct 2002 and Dec 2006 40 pts were randomized. The study was closed prematurely due to poor accrual. Arm A:21 pts, arm B 19 pts. Median age A: 58 yrs (43–73), B: 55 yrs (35–72); PD less vs more than 3 months after 1st-line chemotherapy: A: 18 / 3, B: 17 / 2pts. ECOG PS 0/1 vs 2: A: 17/ 4, B: 14/ 5pts. Pre-treatment with cisplatin: A: 21, B:19 pts. Arm A: 68 cycles administered in 21 pts. Toxicity: (main CTC grade 3/ 4): Nausea 1 pt, vomiting 1 pt, diarrhoea: 5 pts, neutropenic fever: 2 pts, data incomplete 6 pts. In 37% of 19 evaluable pts irinotecan dose was escalated to 350mg/m2. Response (19 pts evaluable): No objective responses, SD 58%, PD 42%. Improvement of tumor related symptoms: 44% of pts in arm A, 5% in arm B. Survival: (evaluable pts arm A 21, arm B 18): median survival arm A: 123 days (95%CI 95–216), arm B 72.5 days (95%CI 41–106); OS: HR=2.85 (95%CI 1.41–5.79), Logrank test (two-sided): p=0.0027. Conclusions: To our knowledge this is the first randomized phase III study investigating 2nd- line chemotherapy in gastric cancer. Irinotecan as 2nd-line chemotherapy significantly prolongs overall survival compared to BSC. 2nd-line chemotherapy can now be considered as a proven option in gastric cancer. [Table: see text]

Activity and survival benefit of second-line chemotherapy (2L-Ctx) in advanced pancreatic adenocarcinoma (APC): Pooled analysis of the literature.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15019-e15019 ◽  
Author(s):  
MinYuen Teo ◽  
Raymond S. McDermott
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Survival Benefit ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase Iii ◽  
Second Line ◽  
Second Line Chemotherapy ◽  
Line Setting ◽  
Line Chemotherapy

e15019 Background: Many clinicians adopt a nihilistic approach to the management of APC. Delivery of 2L-Ctx is relatively uncommon and no recognized standard exists. We sought to examine the published activity of chemotherapy in the 2nd line setting, and the rate of 2L-Ctx delivery and its influence on reported overall survival in 1st line trials. Methods: 1st and 2L-Ctx randomized trials published between 2000 and 2012 were identified from Pubmed, and manuscripts were obtained for data extraction. Pooled weighted objective response rates (ORR) and disease control rates (DCR) were calculated. For 1st line studies, the percentage of patients who received 2L-Ctx were extracted and plotted against reported median overall survival (OS) and post-progression survival (PPS), defined as arithmetic difference between median OS and progression-free survival. Spearman correlation and linear regression were performed. Results: Sixty nine 2L Ctx studies (77 arms, n=2859) were identified. Majority received prior gemcitabine-based chemotherapy. Pooled ORR was 6.6% (95% CI 5.6 – 7.6%) and DCR was 36.7% (34.5 – 38.0%). When only prospective studies were evaluated (42 studies, 48 arms, n=1546), ORR was 5.0% (3.8 – 6.2%) and DCR was 33.9% (31.0 – 36.9%). Exploratory analysis suggested that intensification of gemcitabine-based therapy (ORR: 10.0%; DCR: 54.7%) might be marginally more active than fluoropyrimidine (7.6%; 32.2%) or taxane based 2L-Ctx (5.2%; 33.6%). 28/52 identified 1st line studies (54%) reported the percentage of patients treated with second-line chemotherapy (11 phase II, 28 arms, n=1450; 17 phase III, 33 arms, n=5051). Percentage of 2L-Ctx delivery ranged from 14 – 68% and correlated with OS (r=.49 [.26 – .67], p<.01) and PPS (r=.57 [.36 – .72], p<.01). When phase II studies were excluded, correlation was improved for OS (r=.63 [.35 – .81], p<.01) and PPS (r=.79 [.59 – .89], p<.01). Percentage of locally advanced disease did not correlate with OS/PPS nor affect prior analysis. Conclusions: Whilst awaiting further advancement in the 1st line setting, increased delivery of 2L-Ctx to patients with APC and maintained performance status may offer a survival benefit.

Updated predictive analysis of the WHO-defined molecular subgroups of low-grade gliomas within the high-risk treatment arms of NRG Oncology/RTOG 9802.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2002-2002 ◽  
Author(s):  
Erica Hlavin Bell ◽  
Minhee Won ◽  
Jessica L. Fleming ◽  
Aline P. Becker ◽  
Joseph P. McElroy ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Survival Data ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Rank Test ◽  
Low Grade ◽  
Low Grade Gliomas ◽  
Significant Difference ◽  
Post Hoc

2002 Background: This study sought to update the predictive significance of the three WHO-defined molecular glioma subgroups ( IDHwt, IDHmt/noncodel, and IDHmt/codel) in the subset of specimens available for analysis in NRG Oncology/RTOG 9802, a phase III trial of high-risk low-grade gliomas (LGGs) treated with radiation (RT) with and without PCV after biopsy/surgical resection. Notably, this is the first phase III study to evaluate the predictive value of the WHO subgroups in LGGs using prospectively-collected, well-annotated long-term overall survival data, in a post-hoc analysis. Methods: IDH1/2 mutation status was determined by immunohistochemistry and/or next-generation sequencing. 1p/19q status was determined by Oncoscan and/or 450K methylation data. Treatment effects on overall survival (OS) and progression-free survival (PFS) by marker status were determined by the Cox proportional hazard model and tested using the log-rank test in a secondary and exploratory analysis. Results: Of all the randomized eligible high-risk G2 patients (N = 251) in NRG Oncology/RTOG 9802, 106(42%) patients had tissue available with sufficient quality DNA for profiling. Of these, 80(75%) were IDHmut; 43(41%) were IDHmut/non-co-deleted, 37(35%) were IDHmut/co-deleted, and 26(24%) were IDHwt. Upon univariate analyses, no significant difference in either PFS or OS was observed with the addition of PCV in the IDHwt subgroup. Both the IDHmut/non-co-deleted and IDHmut/co-deleted subgroups were significantly correlated with longer PFS (HR = 0.32; p = 0.003; HR = 0.13; p < 0.001) and OS (HR = 0.38; p = 0.013; HR = 0.21; p = 0.029) in the RT plus PCV arm, respectively. Conclusions: Our analyses suggest that both IDHmut/non-co-deleted and IDHmut/co-deleted subgroups received benefit from treatment with PCV although sample size is limited and analyses are post-hoc. Our results also support the notion that IDHwt high-risk LGG patients do not benefit from the addition of PCV to RT. Funding: U10CA180868, U10CA180822, and U24CA196067. Also, R01CA108633, R01CA169368, RC2CA148190, U10CA180850-01, BTFC, OSU-CCC (all to AC). Clinical trial information: NCT00003375.

FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab as second-line therapy for patients with advanced or metastatic gastroesophageal adenocarcinoma with or without prior docetaxel: Results from the phase II RAMIRIS Study of the AIO.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4514-4514 ◽  
Author(s):  
Sylvie Lorenzen ◽  
Peter C. Thuss-Patience ◽  
Claudia Pauligk ◽  
Eray Goekkurt ◽  
Thomas Jens Ettrich ◽  
...  
Keyword(s):  
Disease Control ◽  
Phase Ii ◽  
Response Rate ◽  
Objective Response ◽  
Disease Control Rate ◽  
Phase Iii ◽  
Response Analysis ◽  
Second Line ◽  
Significant Difference ◽  
Gastroesophageal Adenocarcinoma

4514 Background: Ramucirumab (Ram) as monotherapy or plus paclitaxel is a proven second-line option for advanced gastroesophageal adenocarcinoma (GEA). More and more patients (pts) are pretreated with docetaxel in the perioperative or first-line setting. These pts may benefit more from another, non-cross resistant chemotherapy backbone regimen. This trial evaluates the addition of Ram to FOLFIRI as second line treatment. Methods: This is a multicenter, randomized, investigator initiated, phase II trial. Pts with GEA who have progressed after treatment with a fluoropyrimidine/platinum-containing regimen were randomized 2:1 to either FOLFIRI plus Ram every two weeks (Arm A) or paclitaxel (days 1, 8, 15 of a 28-day cycle) plus Ram every two weeks (Arm B). Major endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and toxicity. Results: 111 pts (median age 61 years, 65% of pts had prior docetaxel therapy) were enrolled and 110 analyzed within intention to treat population (ITT, Arm A, 72; Arm B, 38). In the ITT, there was no significant difference in median OS (A, 6.8 vs. B, 7.6 months, HR 0.94, p = 0.77) and median PFS (A, 4.6 vs. B, 3.6 months, HR 0.72, p = 0.12). For pts with prior docetaxel use (71/110), median PFS was A, 4.3 vs. B, 2.0 months, HR 0.49, p = 0.008 and median OS was A, 7.5 vs. B, 6.4 months, HR 0.71, p = 0.25. In 101 pts with tumor assessment and included in the response analysis, ORR and DCR was 23% and 65% in Arm A and 11% and 60% in Arm B, respectively. 67 pts assessable for response were pre-treated with docetaxel. In these pts, ORR was 24% in Arm A and 9% in Arm B. Disease control rate (DCR) was 67% and 41% for Arm A and B respectively. Both therapies were similarly tolerable, final safety results will be shown. Conclusions: The RAMIRIS trial demonstrated feasibility of the combination of FOLFIRI and Ram. With a response rate of 24% and a median PFS of 4.3 months, docetaxel pre-treated pts seemed to derive pronounced benefit from FOLFIRI-Ram, providing a rationale for a phase III trial, which is currently ongoing. Clinical trial information: NCT03081143 .

ENGOT-en9/LEAP-001: A phase III study of first-line pembrolizumab plus lenvatinib versus chemotherapy in advanced or recurrent endometrial cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6106-TPS6106
Author(s):  
Christian Marth ◽  
Christof Vulsteke ◽  
Maria Jesus Rubio Pérez ◽  
Vicky Makker ◽  
Elena Ioana Braicu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Objective Response ◽  
Phase Iii ◽  
Primary Study ◽  
Antiangiogenic Agents ◽  
Newly Diagnosed ◽  
First Line ◽  
Phase Iii Study ◽  
Previously Treated

TPS6106 Background: The prognosis for endometrial cancer (EC) can be favorable when diagnosed in early stages, but prognosis and overall survival are poor in patients with advanced or recurrent EC. First-line standard of care for patients with advanced or recurrent EC is paclitaxel and carboplatin chemotherapy; however, there is a need for more effective and tolerable therapies. In the phase Ib/II trial KEYNOTE-146, which assessed the PD-1 inhibitor pembrolizumab (pembro) in combination with the multikinase inhibitor lenvatinib, an objective response rate (ORR) of 38% was observed (N=108) in patients with previously treated advanced EC. ENGOT-en9/LEAP-001 (NCT03884101) is a randomized, open-label, active-controlled, phase III study investigating pembro + lenvatinib vs chemotherapy in patients with newly diagnosed advanced or recurrent EC. Methods: Patients with newly diagnosed advanced (stage III-IV) or recurrent EC not previously treated with antiangiogenic agents; systemic chemotherapy (unless within a chemoradiation regimen); PD-1, PD-L1, or PD-L2 inhibitors; or other T-cell receptor–targeted therapies will be eligible. Patients will be randomized 1:1 to receive pembro 200 mg every 3 wk (Q3W) + lenvatinib 20 mg daily or paclitaxel 175 mg/m2 Q3W + carboplatin AUC 6 Q3W. Randomization will be stratified on the basis of proficient vs deficient mismatch repair (pMMR vs dMMR) status. The pMMR population will be further stratified by prior chemoradiation (yes vs no), measurable disease (yes vs no), and ECOG performance status (0 vs. 1). Patients will continue on treatment for up to 35 cycles of pembro vs 7 cycles of chemotherapy or until initiation of a new anticancer treatment, unacceptable adverse events, or withdrawal of consent. Primary study endpoints are progression-free survival (per RECIST v1.1 by blinded independent central review) and overall survival. Secondary study endpoints are ORR, health-related quality of life, safety and tolerability, and lenvatinib pharmacokinetics. Exploratory endpoints will include disease control rate, clinical benefit rate, and duration of response. Enrollment is ongoing. Clinical trial information: NCT03884101.

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