Efficacy of pembrolizumab (pembro) monotherapy versus chemotherapy for PD-L1–positive (CPS ≥10) advanced G/GEJ cancer in the phase II KEYNOTE-059 (cohort 1) and phase III KEYNOTE-061 and KEYNOTE-062 studies.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 427-427 ◽  
Author(s):  
Zev A. Wainberg ◽  
Charles S. Fuchs ◽  
Josep Tabernero ◽  
Kohei Shitara ◽  
Kei Muro ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Durable Response ◽  
Free Survival ◽  
Duration Of Response ◽  
Positive Score ◽  
Combined Positive Score

427 Background: Pts with advanced gastric/gastroesophageal junction (G/GEJ) cancer received pembro monotherapy (200 mg Q3W) 3L+ in cohort 1 of KEYNOTE-059 (NCT02335411), 2L in KEYNOTE-061 (NCT02370498), or 1L in KEYNOTE-062 (NCT02494583). We present efficacy data for patients with PD-L1 combined positive score (CPS) ≥10 tumors in these trials. Methods: In study 059, 46 pts in cohort 1 with PD-L1 CPS ≥10 received pembro. In study 061, 108 pts with PD-L1 CPS ≥10 received pembro (n=53) or chemotherapy (chemo; n=55). In study 062, 182 pts with CPS ≥10 received pembro (n=92) or placebo + chemo (n=90). Efficacy end points included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR). Results: Median follow-up in study 059 was 5.6 mo. Median OS with pembro was 7.9 mo (95% CI, 5.8-11.1), and 12-mo OS was 32.6%. PFS at 6 mo was 17.4%, ORR was 17.4%, and median DOR was 20.9 mo (2.8+ to 34.9+). In study 061, after a median follow-up of 8.8 mo, pembro prolonged OS vs chemo (median 10.4 vs 8.0 mo; HR, 0.64; 95% CI, 0.41-1.02); 12-mo OS was 45.3% for pembro and 23.6% for chemo. Median PFS was 2.7 mo for pembro and 3.4 mo for chemo (HR, 0.86; 95% CI, 0.56-1.33). ORR was 24.5% vs 9.1%, and median DOR was NR (4.1-26.0+) and 6.9 mo (2.6-6.9) for pembro vs chemo. In study 062, median follow-up was 17.4 mo for pembro and 10.8 mo for chemo. Pembro prolonged OS vs chemo (median 17.4 vs 10.8 mo; HR, 0.69; 95% CI, 0.49-0.97); 12-mo OS was 56.5% vs 46.7%. Median PFS was 2.9 mo vs 6.1 mo (HR, 1.09, 95% CI, 0.79-1.49). ORR was 25.0% vs 37.8%, and median DOR was 19.3 mo (1.4+ to 33.6+) vs 6.8 mo (1.5+ to 30.4+) for pembro vs chemo, respectively. Conclusions: Collectively, these data indicate that 1L, 2L, and 3L+ pembro monotherapy showed clinically meaningful efficacy in CPS ≥10, with a more durable response than chemotherapy. Clinical trial information: NCT02335411, NCT02370498, and NCT02494583. [Table: see text]

Efficacy of avelumab plus axitinib (A + Ax) versus sunitinib (S) by number of IMDC risk factors and tumor sites at baseline in advanced renal cell carcinoma (aRCC): Extended follow-up results from JAVELIN Renal 101.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 302-302
Author(s):  
Yoshihiko Tomita ◽  
Robert J. Motzer ◽  
Toni K. Choueiri ◽  
Brian I. Rini ◽  
Hideaki Miyake ◽  
...  
Keyword(s):  
Risk Factors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Risk Groups ◽  
Phase Iii ◽  
Once Daily ◽  
Free Survival ◽  
To Receive

302 Background: In the phase III JAVELIN Renal 101 trial (NCT02684006), A + Ax demonstrated progression-free survival (PFS) and objective response rate (ORR) benefit across IMDC risk groups (favorable, intermediate, and poor) vs S in patients with previously untreated aRCC. Here we report efficacy of A + Ax vs S by number of IMDC risk factors (0, 1, 2, 3, and 4-6) and target tumor sites (1, 2, 3, and ≥4) at baseline from the second interim analysis of overall survival (OS). Methods: Patients were randomized 1:1 to receive A 10 mg/kg intravenously every 2 wk + Ax 5 mg orally twice daily or S 50 mg orally once daily for 4 wk (6-wk cycle). PFS and ORR per independent central review (RECIST 1.1) and OS were assessed. Results: At data cut-off (Jan 2019), median (m) follow-up for OS and PFS was 19.3 vs 19.2 mo and 16.8 vs 15.2 mo for the A + Ax vs S arm, respectively. The table shows OS, PFS, and ORR by number of IMDC risk factors and target tumor sites at baseline. A + Ax generally demonstrated efficacy benefit vs S across subgroups. Conclusions: With extended follow-up, A + Ax generally demonstrated efficacy benefit vs S across the number of IMDC risk factors and tumor sites at baseline in aRCC. OS was still immature; follow-up for the final analysis is ongoing. Clinical trial information: NCT02684006 . [Table: see text]

Nivolumab (NIVO) + low-dose ipilimumab (IPI) as first-line (1L) therapy in microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Two-year clinical update.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4040-4040 ◽  
Author(s):  
Heinz-Josef Lenz ◽  
Sara Lonardi ◽  
Vittorina Zagonel ◽  
Eric Van Cutsem ◽  
M. Luisa Limon ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Low Dose ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Duration Of Response ◽  
Therapy Option ◽  
Grade 3

4040 Background: In the phase 2 CheckMate 142 trial, NIVO + low-dose IPI had robust, durable clinical benefit and was well tolerated as 1L therapy for MSI-H/dMMR mCRC (median follow-up 13.8 months [mo; range, 9–19]; Lenz et al. Ann Oncol 2018;29:LBA18). Longer follow-up is presented here. Methods: Patients (pts) with MSI-H/dMMR mCRC and no prior treatment for metastatic disease received NIVO 3 mg/kg Q2W + low-dose IPI 1 mg/kg Q6W until disease progression or discontinuation. The primary endpoint was investigator-assessed (INV) objective response rate (ORR) per RECIST v1.1. Results: In 45 pts with median follow-up of 29.0 mo, ORR (95% CI) increased to 69% (53–82) (Table) from 60% (44.3–74.3); complete response (CR) rate increased to 13% from 7%. The concordance rate of INV and blinded independent central review was 89%. Median duration of response (DOR) was not reached (Table). Median progression-free survival (PFS) and overall survival (OS) were not reached, and 24-mo rates were 74% and 79%, respectively (Table). Nineteen pts discontinued study treatment without subsequent therapy. An analysis of tumor response post discontinuation will be presented. Ten (22%) pts had grade 3–4 treatment-related adverse events (TRAEs); 3 (7%) had grade 3–4 TRAEs leading to discontinuation. Conclusions: NIVO + low-dose IPI continued to show robust, durable clinical benefit with a deepening of response, and was well tolerated with no new safety signals identified with longer follow-up. NIVO + low-dose IPI may represent a new 1L therapy option for pts with MSI-H/dMMR mCRC. Clinical trial information: NTC02060188 . [Table: see text]

scholarly journals Primary Clinical Response of Relmacabtagene Autoleucel in Adults with Relapsed/Refractory Follicular Lymphoma (r/r FL) in China

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2434-2434
Author(s):  
Yuqin Song ◽  
Zhitao Ying ◽  
Haiyan Yang ◽  
Ye Guo ◽  
Wenyu Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Duration ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose ◽  
Free Survival ◽  
Duration Of Response

Abstract Background Most patients (pts) with r/r FL remain incurable and eventually relapse or progress. Previously, a Ph1 study of relma-cel (NCT03344367) had demonstrated preliminary safety and efficacy in r/r B-NHL pts, including those with r/r FL. A Ph2 pivotal study in r/r FL pts had been enrolled and preliminary efficacy, safety and PK was presented. Methods Adult pts were eligible with histologically confirmed grade (Gr)1-3a r/r FL on the basis of the 2016 WHO Classification, having failed ≥ 2-line prior therapies or relapsed after auto-HSCT, without allogeneic transplant within 90 days or primary central nervous system (CNS) lymphoma, and with ECOG performance score of 0-1. Pts were randomized to receive either 100×10 6 (low dose) or 150×10 6 (high dose) relma-cel (1:1) following fludarabine 25 mg/m 2 & cyclophosphamide 250 mg/m 2 daily×3. Pts were evaluated for efficacy (Cheson, 2014), toxicity (cytokine release syndrome [CRS] by Lee 2014, and others by CTCAE v4.03), and PK (by qPCR and flow cytometry). Primary endpoint was complete response rate (CRR). Secondary endpoints included objective response rate (ORR), frequency/severity of AEs, duration of response (DOR), duration of complete response (DoCR), duration of partial response (DoPR), time to primary remission (TTR), time to primary complete remission (TTCR), progression free survival (PFS), overall survival (OS), and CAR-T cell expansion. Disease response was by investigator assessment, a sensitivity analysis was also conducted using an independent review committee. Results Between June 2018 and June 2021, 28 r/r FL pts were enrolled and treated. As of the data cut-off of June 11, 2021, 20 pts were treated with relma-cel with ≥ 1 month of follow-up. Among these 20 pts, the median age was 54.5 years (range, 36-71), 50% of pts were male, 85% had ECOG 0, 10% had a sum of perpendicular diameters (SPD) ≥ 5000 mm 2, and 36% (5/14) had a FLIPI2 score≥ 3. Pts had received a median of 3.5 prior lines of therapy, 6 (30%) pts had received at least five lines of treatment and 65% were refractory to last prior treatment, 85% were relapsed, 50% were both relapsed and refractory. Relma-cel was successfully manufactured in all pts. Best ORR was 100% (19/19), and best CRR was 95% (18/19). For the mITT (n=19, one pt who developed gastric adenocarcinoma, was excluded, but also achieved CR), ORR at 1 month was 100%(19/19) and CRR was 63% (12/19). CRR at 3 months for 17 pts > 3 months post treatment, was 82%(14/17). At a median follow-up of 8.9 months, the median duration of response [DOR], progression-free survival (PFS) and overall survival (OS) were not reached. Twenty pts who received relma-cel were evaluable for safety. Gr ≥3 AEs related to relma-cel occurred in 80% of pts, most commonly neutrophil count decreased (35%), lymphocyte count decreased (30%) and white blood cell count decreased (25%). CRS occurred in 35% (all Gr 1), and only 2 pts received tocilizumab. Median CRS onset was 7 days (range, 5-9), with median duration of 5 days. Two (10%) pts experience neurotoxicity (NT), both Gr 1, with onsets of 4 and 9 days, and duration of 25 and 7 days, respectively. No deaths occurred. Safety data, tocilizumab/steroids usage and PK parameters are shown in the Table. Conclusion With median follow-up of 8.9 months, relma-cel treatment in r/r FL pts had resulted in high tumor remission rates and a manageable toxicity profile in the first 20 pts treated. Data for additional patients will be presented. Table： The summary of AEs (AE, TEAE, CRS, NT), the usage of tocilizumab/steroids and PK Parameters Figure 1 Figure 1. Disclosures Yang: JW Therapeutics: Current Employment. Zhang: JW Therapeutics: Current Employment. Ma: JW Therapeutics: Current Employment. Zhou: JW Therapeutics: Current Employment. Zheng: JW Therapeutics: Current Employment.

The NIBIT-M1 trial: Activity of ipilimumab plus fotemustine in patients with melanoma and brain metastases.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8529-8529 ◽  
Author(s):  
Michele Maio ◽  
Alessandro Testori ◽  
Paolo Antonio Ascierto ◽  
Ruggero Ridolfi ◽  
Mario Santinami ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Objective Response ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Free Survival ◽  
Brain Radiotherapy ◽  
Grade 3

8529 Background: Patients (pts) with metastatic melanoma (MM) often develop treatment-resistant brain metastases (mets). Treatment includes fotemustine (FTM), which crosses the blood-brain barrier. Ipilimumab (ipi) has shown activity in pts with MM and asymptomatic brain mets (Heller et al. ASCO 2011; abs 8581). In the phase II NIBIT-M1 trial, MM pts with asymptomatic brain mets were eligible for treatment with ipi plus FTM. Here, data from this pt subset are reported. Methods: Eligible pts received induction therapy with ipi 10 mg/kg every 3 wks (Q3W) x4 and FTM 100 mg/m2 weekly for 3 wks, followed by ipi Q12W from Week (W) 24 and FTM Q3W from W9. The primary objective was the immune-related (ir) disease control rate (irDCR: complete/partial response [CR/PR] or stable disease [SD] using the ir response criteria). Secondary objectives included ir objective response rate (ORR) and progression-free survival (PFS); overall survival (OS), and safety. Tumor assessments were performed Q8W from W12 to W36 and Q12W thereafter. Results: Among 86 enrolled pts, 20 had brain mets. Of these, 7 had prior whole brain radiotherapy (n=4) or radiosurgery (n=3). As of December 2011, the irDCR was 50% (10/20; 95% CI, 27.2–72.8%) with an irORR of 40% (95% CI, 19.1–63.9%: 2 CRs and 6 PRs). Pts with irDC also had stability/reduction (n=5) or disappearance (n=5) of brain mets. Among pts with progressive disease, all but one had progression in the brain. With median follow-up of 8.3 months (range: 0.4–16.9), median irPFS was 4.6 months (95% CI, 0.7–12.3). The 1-year OS rate was 52.9% (95% CI, 26.6–79.2); median OS was not reached. Induction with ipi and FTM was completed by 55% and 85% pts, respectively. Grade 3/4 drug-related adverse events (AEs) occurred in 60% pts; most commonly myelotoxicity (50%), increased ALT/AST (5%) and gastrointestinal (5%). AEs were generally manageable and reversible per protocol guidance. CNS AEs of any grade (i.e., haemorrhage, headache and seizure) occurred in 25% pts (grade 3/4 in 2 pts) and were attributed to disease progression. Conclusions: The combination of ipi plus FTM is active and safe in pts with MM and brain mets, regardless of prior treatment, and will be further explored in the phase III NIBIT-M2 trial.

Pembrolizumab in previously treated metastatic esophageal cancer: Longer term follow-up from the phase 2 KEYNOTE-180 Study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4032-4032 ◽  
Author(s):  
Ken Kato ◽  
Takashi Kojima ◽  
Daniel Hochhauser ◽  
Jaafar Bennouna ◽  
Antoine Hollebecque ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Phase 2 ◽  
Open Label ◽  
Heavily Pretreated ◽  
Positive Score ◽  
Previously Treated ◽  
Combined Positive Score

4032 Background: In the phase 2, open-label, KEYNOTE-180 (NCT02559687) study, after a median follow-up of 5.8 months, pembrolizumab (pembro) provided antitumor activity with durable responses in pts with previously treated, advanced/metastatic adenocarcinoma (EAC) including Siewert type 1 adenocarcinoma of the gastroesophageal junction or squamous cell carcinoma (ESCC) of the esophagus. Here we present results of an additional 10 months of follow-up. Methods: Eligible pts with metastatic esophageal cancer, ≥2 prior lines of therapy, and tumor samples evaluable for biomarker expression, received pembro 200 mg Q3W for up to 2 years, or until disease progression, unacceptable toxicity, or withdrawal. Tumor response was assessed Q9W (RECISTv1.1, central review). PD-L1+ pts had combined positive score ≥10 using IHC (22C3 antibody). Primary endpoint was objective response rate (ORR). Secondary endpoints included safety, DOR, PFS, and OS. Results: Of 121 pts enrolled, 63 (52%) had ESCC and 58 (48%) had PD-L1+ (combined positive score ≥10) tumors. As of July 30, 2018, median follow-up duration, from randomization to data cutoff, was 5.8 mo (range, 0.2 mo to 27.8+ mo). ORR (CR+PR) was 10% (95% CI, 5%-17%); 2 (2%) CR,10 (8%) PR, 25 (21%) SD. Median DOR was not reached ([NR] range, 2.1 mo to 25.1+ mo). Median PFS was 2 mo (95% CI, 1.9%-2.1%) with 9-mo PFS rate of 9%. Median OS was 5.8 mo (4.5-7.2) with 12 mo OS rate of 27%. In ESCC, ORR was 14% (95% CI, 7%-25%); 2 (3%) CR, 7 (11%) PR, with median DOR NR (range, 4.2 mo to 25.1+ mo). In EAC, ORR was 5% (95% CI, 1-14); 3 PR, with median DOR NR (range, 2.1 mo to 15.6+ mo). In PD-L1+ pts, ORR was 14% (95% CI, 6%-25%); 1 (2%) CR, 7 (12%) PR with median DOR NR (range, 4.2 mo to 25.1+ mo). In PD-L1- pts ORR was 6% (95% CI, 2%-16%); 1 (2%) CR, 3 (5%) PR; median DOR NR (range, 2.1 mo to 17.3+ mo). Overall, 19 (16%) pts had treatment-related grade 3-5 AEs. Seven (6%) pts discontinued due to a treatment-related AE. There was one treatment-related death from pneumonitis. Conclusions: Pembro continued to provide durable clinical benefit with a manageable safety profile for pts with heavily pretreated esophageal cancer, with conversions of PR to CR observed. Clinical trial information: NCT02559687.

Pembrolizumab versus paclitaxel for previously treated patients with PD-L1–positive advanced gastric or gastroesophageal junction cancer (GC): Update from the phase III KEYNOTE-061 trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4503-4503 ◽  
Author(s):  
Charles S. Fuchs ◽  
Mustafa Özgüroğlu ◽  
Yung-Jue Bang ◽  
Maria Di Bartolomeo ◽  
Mario Mandalà ◽  
...  
Keyword(s):  
Standard Dose ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
Analysis Data ◽  
Phase Iii ◽  
Second Line ◽  
Primary Analysis ◽  
Gastroesophageal Junction Cancer ◽  
Duration Of Response

4503 Background: KEYNOTE-061 ( NCT02370498) is a global phase 3 study of pembrolizumab vs paclitaxel as second-line therapy for GC. At the time of primary analysis (data cutoff: Oct 26, 2017), in patients with PD-L1–positive status (combined positive score [CPS] ≥1), pembrolizumab did not significantly prolong overall survival (OS) vs paclitaxel (9.1 months vs 8.3 months) but did elicit a longer duration of response (DOR) and a favorable safety profile vs paclitaxel. We present results of KEYNOTE-061 in patients with CPS ≥1, ≥5, and ≥10 after 2 additional years of follow-up (cutoff: Oct 7, 2019). Methods: Adult patients with GC that progressed after platinum + fluoropyrimidine chemotherapy were randomly assigned 1:1 to pembrolizumab 200 mg Q3W for up to 35 cycles (~2 y) or standard-dose paclitaxel. OS and progression-free survival (PFS) in the CPS ≥1 population were the primary end points. Comparisons were made using stratified log-rank tests. Results: At the time of this analysis, 366/395 patients with CPS ≥1 had died (92.6%). Pembrolizumab prolonged OS vs paclitaxel in PD-L1–positive patients (Table). No significant differences appeared between groups in PFS (Table). Objective response rate (ORR) was higher for pembrolizumab in the CPS ≥10 group, and DOR was longer with pembrolizumab using all CPS cutoffs (Table). There were fewer drug-related adverse events (AEs) with pembrolizumab than paclitaxel in the overall population (53% vs 84%). Conclusions: This long-term analysis found that second-line pembrolizumab prolonged OS among patients with PD-L1–positive GC and led to fewer drug-related AEs vs paclitaxel. Clinical trial information: NCT02370498 . [Table: see text]

scholarly journals The Efficacy of TACE Combined With Lenvatinib Plus Sintilimab in Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Fei Cao ◽  
Yi Yang ◽  
Tongguo Si ◽  
Jun Luo ◽  
Hui Zeng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Once Daily ◽  
Free Survival ◽  
Unresectable Hepatocellular Carcinoma ◽  
Primary Endpoints ◽  
Duration Of Response ◽  
Modified Recist

ObjectiveTo assess the efficacy and safety of transarterial Chemoembolization (TACE) combined with lenvatinib plus sintilimab in unresectable hepatocellular carcinoma (HCC).Patients and MethodsThe data of patients with unresectable HCC administered a combination therapy with TACE and lenvatinib plus sintilimab were retrospectively assessed. Patients received lenvatinib orally once daily 2 weeks before TACE, followed by sintilimab administration at 200 mg intravenously on day 1 of a 21-day therapeutic cycle after TACE. The primary endpoints were objective response rate (ORR) and duration of response (DOR) by the modified RECIST criteria.ResultsMedian duration of follow-up was 12.5 months (95%CI 9.1 to 14.8 months). ORR was 46.7% (28/60). Median DOR in confirmed responders was 10.0 months (95%CI 9.0-11.0 months). Median progression-free survival (PFS) was 13.3 months (95%CI 11.9-14.7 months). Median overall survival (OS) was 23.6 months (95%CI 22.2-25.0 months).ConclusionsTACE combined with lenvatinib plus sintilimab is a promising therapeutic regimen in unresectable hepatocellular carcinoma.

Phase III Randomized, Intergroup Trial Assessing Imatinib Mesylate At Two Dose Levels in Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors Expressing the Kit Receptor Tyrosine Kinase: S0033

2008 ◽  
Vol 26 (4) ◽  
pp. 626-632 ◽  
Author(s):  
Charles D. Blanke ◽  
Cathryn Rankin ◽  
George D. Demetri ◽  
Christopher W. Ryan ◽  
Margaret von Mehren ◽  
...  
Keyword(s):  
Overall Survival ◽  
Gastrointestinal Stromal Tumors ◽  
Standard Dose ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
High Dose ◽  
Free Survival ◽  
Stromal Tumors

PurposeTo assess potential differences in progression-free or overall survival when imatinib mesylate is administered to patients with incurable gastrointestinal stromal tumors (GIST) at a standard dose (400 mg daily) versus a high dose (400 mg twice daily).Patients and MethodsPatients with metastatic or surgically unresectable GIST were eligible for this phase III open-label clinical trial. At registration, patients were randomly assigned to either standard or high-dose imatinib, with close interval follow-up. If objective progression occurred by Response Evaluation Criteria in Solid Tumors, patients on the standard-dose arm could reregister to the trial and receive the high-dose imatinib regimen.ResultsSeven hundred forty-six patients with advanced GIST from 148 centers across the United States and Canada were enrolled onto this trial in 9 months. With a median follow-up of 4.5 years, median progression-free survival was 18 months for patients on the standard-dose arm, and 20 months for those receiving high-dose imatinib. Median overall survival was 55 and 51 months, respectively. There were no statistically significant differences in objective response rates, progression-free survival, or overall survival. After progression on standard-dose imatinib, 33% of patients who crossed over to the high-dose imatinib regimen achieved either an objective response or stable disease. There were more grade 3, 4, and 5 toxicities noted on the high-dose imatinib arm.ConclusionThis trial confirms the effectiveness of imatinib as primary systemic therapy for patients with incurable GIST but did not show any advantage to higher dose treatment. It appears reasonable to initiate therapy with 400 mg daily and to consider dose escalation on progression of disease.

scholarly journals The Efficacy of Ramucirumab in the Treatment of Gastric or Gastroesophageal Junction Cancer: A Meta-Analysis of RCTs

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Hongqiong Yang ◽  
Yaojun Zhou ◽  
Liangzhi Wang ◽  
Tianyi Gu ◽  
Mengjia Lv ◽  
...  
Keyword(s):  
Response Rate ◽  
Meta Analysis ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
First Line ◽  
Free Survival ◽  
Gastroesophageal Junction Cancer ◽  
Line Chemotherapy

Five electronic databases were searched for eligible records. Outcomes were presented and analyzed according to the objective response rate (ORR), progression-free survival (PFS) rate, and overall survival (OS) rate. Five records involving 2,024 participants were included in the study. The pooled analysis of OS and PFS were longer with ramucirumab (RAM) therapy than without RAM for OS (odds ratio OR = 0.90 , 95% confidence interval CI = 0.82 – 1.00 , p = 0.05 ) and PFS ( OR = 0.74 , 95 % CI = 0.57 – 0.96 , p = 0.02 ). Moreover, compared with the current first-line chemotherapy, the OS ( OR = 0.93 , 95 % CI = 0.83 – 1.04 , p = 0.19 ) and PFS ( OR = 0.82 , 95 % CI = 0.64 – 1.06 , p = 0.13 ) results were not significantly higher with RAM. The ORRs of the patients in the RAM therapy groups were significantly higher than those in the groups without RAM ( OR = 1.40 , 95 % CI = 1.14 – 1.73 , p = 0.001 ).

Nivolumab (NIVO) plus ipilimumab (IPI) or NIVO plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): First results of the CheckMate 648 study.

2021 ◽  
Vol 39 (18_suppl) ◽  
pp. LBA4001-LBA4001
Author(s):  
Ian Chau ◽  
Yuichiro Doki ◽  
Jaffer A. Ajani ◽  
Jianming Xu ◽  
Lucjan Wyrwicz ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Primary Endpoints ◽  
First Results ◽  
Duration Of Response ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Previously Treated Patients

LBA4001 Background: NIVO demonstrated superior overall survival (OS) vs chemo in previously treated patients (pts) with ESCC (ATTRACTION-3). We report OS and progression-free survival (PFS) from CheckMate 648, the first global phase III study to evaluate both an immuno-oncology (I-O)/chemo combination and an I-O/I-O combination in advanced ESCC. Methods: Adults with previously untreated, unresectable advanced, recurrent or metastatic ESCC were enrolled regardless of tumor cell PD-L1 expression. Pts were randomized to NIVO (240 mg Q2W) + chemo (fluorouracil + cisplatin Q4W), NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), or chemo alone. Primary endpoints for both comparisons were OS and PFS per blinded independent central review (BICR) in pts with tumor cell PD-L1 ≥ 1%. Hierarchically tested secondary endpoints included OS and PFS in all randomized pts. Results: 970 pts were randomized to NIVO + chemo, NIVO + IPI, and chemo arms (49% with tumor cell PD-L1 ≥ 1%). With 13 months (mo) minimum follow-up, NIVO + chemo and NIVO + IPI led to statistically significant improvement in OS vs chemo in pts with tumor cell PD-L1 ≥ 1% and all randomized pts (Table). Statistically significant PFS benefit was also observed for NIVO + chemo vs chemo (HR 0.65 [98.5% CI 0.46–0.92]; P = 0.0023) in pts with tumor cell PD-L1 ≥ 1%. PFS in NIVO + IPI vs chemo in pts with tumor cell PD-L1 ≥ 1% did not meet the prespecified boundary for significance. The objective response rate (per BICR) was 53% (NIVO + chemo), 35% (NIVO + IPI), and 20% (chemo) in pts with tumor cell PD-L1 ≥ 1% and in all randomized pts was 47%, 28%, and 27%, respectively; longer median (95% CI) duration of response was observed vs chemo for pts with tumor cell PD-L1 ≥ 1%: 8.4 (6.9–12.4), 11.8 (7.1–27.4), and 5.7 (4.4–8.7) mo and for all randomized pts: 8.2 (6.9–9.7), 11.1 (8.3–14.0), and 7.1 (5.7–8.2) mo, respectively. No new safety signals were identified (Table). Conclusions: NIVO plus chemo and NIVO plus IPI both demonstrated superior OS vs chemo, along with durable objective responses and acceptable safety, in pts with advanced ESCC, and each represents a potential new 1L treatment option. Clinical trial information: NCT03143153. [Table: see text]

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