Efficacy and tolerability of bevacizumab (BEV) plus capecitabine and cisplatin (XP) in Chinese patients (pts) with locally advanced or metastatic gastric/gastroesophageal junction cancer (AGC): Results from the AVATAR study.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 73-73 ◽  
Author(s):  
Lin Shen ◽  
Jin Li ◽  
Jian-Ming Xu ◽  
Hong-Ming Pan ◽  
Guanghai Dai ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Chinese Patients ◽  
Double Blind Study ◽  
Double Blind ◽  
Gastroesophageal Junction Cancer ◽  
The Difference ◽  
Grade 3

73 Background: In the AVAGAST study, chemotherapy (fluoropyrimidine and cisplatin) + BEV did not significantly improve overall survival (OS) vs. chemotherapy + placebo. Geographic differences in efficacy were observed, but only 12 Chinese pts were included. AVATAR, a study similar in design to AVAGAST, is a randomized double-blind study conducted exclusively in China in pts with AGC. Methods: Pts aged >18 years with gastric adenocarcinoma were randomized 1:1 to XP + BEV 7.5 mg/kg or placebo + XP. The primary objective was OS; secondary objectives included progression-free survival (PFS) and safety. Results: Baseline characteristics of the 202 pts were well balanced. The primary efficacy endpoint of improved OS in the BEV arm was not met (HR 1.11, 95% CI 0.79–1.56; p=0.5567; see table ). BEV + XP was well tolerated. Grade 3–5 adverse events (AEs) and serious AEs were 60% and 19% for BEV and 68% vs. 21% for placebo, respectively. Grade 3–5 AEs of special interest with BEV occurred in 8% of BEV pts and 15% of placebo pts; the difference was mainly due to grade 3–5 haemorrhage (BEV 4%, placebo 12%). Conclusions: Addition of BEV to XP in Chinese pts with AGC did not significantly improve outcomes in AVATAR. The results from AVATAR are consistent with the findings seen in the Asian sub-population of the previous AVAGAST study. [Table: see text]

AVAGAST: A randomized, double-blind, placebo-controlled, phase III study of first-line capecitabine and cisplatin plus bevacizumab or placebo in patients with advanced gastric cancer (AGC).

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA4007-LBA4007 ◽  
Author(s):  
Y. Kang ◽  
A. Ohtsu ◽  
E. Van Cutsem ◽  
S. Y. Rha ◽  
A. Sawaki ◽  
...  
Keyword(s):  
Randomized Study ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Disease Status ◽  
Primary Objective ◽  
Geographical Region ◽  
Phase Iii ◽  
Asia Pacific ◽  
Double Blind

LBA4007 Background: The median survival for patients (pts) with AGC in most phase III studies is less than 1 year. The addition of bevacizumab (bev) to chemotherapy (chemo) is supported by a strong preclinical rationale and by phase II evaluation. AVAGAST is the first randomized study to compare the efficacy and safety of bev + chemo vs placebo + chemo. Methods: Pts with inoperable, locally advanced or metastatic stomach/gastroesophageal junction adenocarcinoma with no prior therapy were randomized 1:1 to capecitabine (cape, or 5-FU) + cisplatin (cis) and either bev (7.5 mg/kg iv) or placebo q3w. Stratification variables: geographical region, fluoropyrimidine treatment, disease status. Cis was given for 6 cycles; bev/placebo + cape/5-FU were given until disease progression or unmanageable toxicity. Primary objective: compare overall survival (OS); secondary objectives: compare progression-free survival (PFS), overall response rate (ORR), and safety (as overseen by an independent DSMB). Results: From Sep 2007 to Dec 2008, 774 pts were enrolled. Treatment arms were balanced. Approx 95% of pts were metastatic. Two-thirds of pts were male, 49% of pts were from Asia/Pacific, 32% from Europe and 19% from the Americas. Median OS was 10.1 months with chemo + placebo and 12.1 months with chemo + bev in the intent-to-treat population (HR 0.87; p=0.1002). Median OS according to geographical region was 6.8 vs. 11.5 months (HR 0.63) in the Americas, 8.6 vs. 11.1 months (HR 0.85) in Europe and 12.1 vs. 13.9 months in Asia-Pacific (HR 0.97). Secondary endpoints and AEs of special interest for Bev are summarized below ( Table ). Conclusions: While the primary endpoint was not met (median OS HR 0.87; p=0.1002), there was a significant improvement in PFS and ORR and an acceptable safety profile for bev + chemo in patients with AGC. [Table: see text] [Table: see text]

An international, double-blind, randomized, placebo-controlled phase III trial (EXAM) of cabozantinib (XL184) in medullary thyroid carcinoma (MTC) patients (pts) with documented RECIST progression at baseline.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5508-5508 ◽  
Author(s):  
Patrick Schoffski ◽  
Rossella Elisei ◽  
Stefan Müller ◽  
Marcia S. Brose ◽  
Manisha H. Shah ◽  
...  
Keyword(s):  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Double Blind ◽  
Efficacy Measure ◽  
Independent Review ◽  
Phase Iii Study ◽  
Grade 3

5508 Background: MTC arises from parafollicular cells of the thyroid gland, accounts for 5-8% of thyroid cancers and represents an unmet medical need. Cabozantinib (cabo) is an oral inhibitor of MET, VEGFR2, and RET. We conducted a phase III study of cabo vs placebo (P) in pts with progressive, unresectable, locally advanced or metastatic MTC. Methods: Eligible pts were required to have documented RECIST progression within 14 months of screening. The primary efficacy measure was progression-free survival (PFS) as assessed by an independent review facility (IRF) using RECIST. Secondary efficacy measures included objective response rate (ORR) and overall survival (OS). The study has 90% power to detect a 75% increase in PFS and 80% power to detect a 50% increase in OS. Tumor assessments occurred every 12 weeks. Crossover between treatment arms was not allowed. Results: Between Sept 2008 and Feb 2011, 330 pts (median age 55 yrs; 67% male; 96% measureable disease; RET mutation status: pos 48%; neg 12%; unknown 39%; prior TKI exposure: yes 21%, no 78%, unknown 2%) were randomized 2:1 to cabo (140 mg free base [175 mg salt form] qd; n=219) or P (n=111). The planned primary PFS analysis included events through the date of the 138th event. As of 15June2011, 44.7% of pts on cabo and 13.5% on P were still receiving study treatment. Statistically significant PFS prolongation of 7.2 mo was observed; median PFS for cabo was 11.2 mo vs 4.0 mo for P (HR 0.28, 95% CI 0.19-0.40, p<0.0001). PFS results favored the cabo group across subset analyses including RET status and prior TKI use. ORR was 28% for cabo vs 0% for P (p<0.0001). An interim analysis of OS (44% of the 217 required events) did not show a difference between cabo and P. The most frequent grade ≥3 adverse events (cabo vs P) were diarrhea (15.9 vs 1.8%), palmar-plantar erythrodysesthesia (12.6 vs 0%), fatigue (9.3 vs 2.8%), hypocalcemia (9.3 vs 0%), and hypertension (7.9 vs 0%). Conclusions: This phase III study met its primary objective of demonstrating substantial PFS prolongation with cabo vs. P in a patient population with MTC and documented progressive disease in need of therapeutic intervention.

RAINBOW: A global, phase 3, double-blind study of ramucirumab (RAM) plus paclitaxel (PTX) versus placebo (PL) plus PTX in the treatment of advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy—An age-group analysis.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 11-11 ◽  
Author(s):  
Kei Muro ◽  
Gyorgy Bodoky ◽  
Alvydas Cesas ◽  
Yee Chao ◽  
Philip Clingan ◽  
...  
Keyword(s):  
Disease Progression ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Group Analysis ◽  
Age Groups ◽  
Progression Free Survival ◽  
Double Blind Study ◽  
Double Blind ◽  
Grade 3 ◽  
Ecog Ps

11 Background: RAM is a human IgG1 monoclonal antibody VEGF-R2 antagonist. The RAINBOW trial demonstrated that RAM added to PTX significantly improved overall survival (OS), progression free survival (PFS), and objective response rates (ORR) in 2nd-line gastric and GEJ adenocarcinoma patients (pts). Outcomes are reported by pts aged <65 and ≥65 yrs. Methods: Pts with advanced gastric and GEJ adenocarcinoma after disease progression on platinum- and fluoropyrimidine-based chemotherapy were randomized 1:1 to receive RAM (8 mg/kg) or placebo (PL) on days 1 and 15 plus PTX 80 mg/m2IV on days 1, 8, and 15 of a 28-day cycle. Eligible pts had ECOG PS ≤ 1 and adequate organ function. OS was the primary endpoint. Secondary endpoints included PFS, ORR, and safety. Results: Baseline characteristics were generally well balanced. Outcomes are summarized in the Table. The incidence of Grade ≥3 adverse events (AEs) was higher in the RAM+PTX arms for both age groups and similar across age groups. Grade ≥3 AEs occurring in ≥10% of pts and at higher rate in the RAM+PTX arm, and febrile neutropenia are shown in the Table. Conclusions: RAM+PTX conferred similar improvements over PL+PTX for OS, PFS, and ORR in both age groups. Toxicity profiles were similar in both groups, although a relatively higher incidence of Grade ≥3 neutropenia and leukopenia in pts ≥65 years was noted. [Table: see text]

JUPITER-02: Randomized, double-blind, phase III study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC).

2021 ◽  
Vol 39 (18_suppl) ◽  
pp. LBA2-LBA2
Author(s):  
Rui-hua Xu ◽  
Hai-Qiang Mai ◽  
Qiu-Yan Chen ◽  
Dongping Chen ◽  
Chaosu Hu ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Double Blind ◽  
Grade 3 ◽  
First Line Treatment

LBA2 Background: Gemcitabine-cisplatin (GP) chemotherapy is the standard 1st line treatment for locally advanced, recurrent or metastatic (r/m) NPC. Toripalimab, a humanized IgG4K monoclonal antibody specific for PD-1, provided durable responses in patients (pts) with r/m NPC as monotherapy in the ≥2nd line setting (POLARIS-02 study). The results of JUPITER-02, a randomized, placebo-controlled, double-blinded Phase III trial of toripalimab in combination with GP chemotherapy as first-line treatment for r/m NPC are summarized. Methods: Pts with advanced NPC with no prior chemotherapy in the r/m setting were randomized (1:1) to receive toripalimab 240 mg or placebo d1 in combination with gemcitabine 1000 mg/m2 d1, d8 and cisplatin 80 mg/m2 d1 every 3 weeks (Q3W) for up to 6 cycles, followed by monotherapy with toripalimab or placebo Q3W until disease progression, intolerable toxicity, or completion of 2 years of treatment. Stratification factors were ECOG PS (0 vs. 1) and extent of disease (recurrent vs. primary metastatic) at enrollment. Progression-free survival (PFS) and response were assessed by independent review committee (IRC) per RECIST v1.1. The primary endpoint was PFS by IRC in the ITT population. Secondary end points included ORR, DOR and OS. There was one prespecified interim analysis of PFS at 130 PFS events with a planned final analysis at 200 PFS events. Results: 289 pts were randomized: 146 to the toripalimab arm and 143 to the placebo arm. By May 30, 2020 as the interim analysis cutoff date, the median treatment duration was 39 weeks in the toripalimab arm and 36 weeks in the placebo arm. A significant improvement in PFS was detected for the toripalimab arm compared to the placebo arm (HR = 0.52 [95% CI: 0.36-0.74] two-sided p = 0.0003), with median PFS of 11.7 vs. 8.0 months. The 1-year PFS rates were 49% and 28% respectively. An improvement in PFS was observed across relevant subgroups, including all PD-L1 subgroups. The ORR was 77.4% vs. 66.4% (P = 0.033) and the median DOR was 10.0 vs. 5.7 months (HR = 0.50 [95% CI: 0.33-0.78]). As of Jan 15, 2021, OS was not mature, with 25 deaths in the toripalimab arm and 35 in the placebo arm (HR = 0.68 [95% CI: 0.41-1.14], P = 0.14). The incidence of Grade ≥3 adverse events (AEs) (89.0% vs 89.5%); AEs leading to discontinuation of toripalimab/placebo (7.5% vs 4.9%); and fatal AEs (2.7% vs 2.8%) were similar between two arms; however, immune-related (irAEs) (39.7% vs. 18.9%) and Grade ≥3 irAEs (7.5% vs. 0.7%) were more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to GP chemotherapy as 1st-line treatment for pts with advanced NPC provided superior PFS and ORR and longer DOR than GP alone with a manageable safety profile. These results support the use of toripalimab with GP chemotherapy as the new standard care for this population. Clinical trial information: NCT03581786.

Vandetanib versus erlotinib in patients with advanced non-small cell lung cancer (NSCLC) after failure of at least one prior cytotoxic chemotherapy: A randomized, double-blind phase III trial (ZEST)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8009-8009
Author(s):  
R. B. Natale ◽  
S. Thongprasert ◽  
F. A. Greco ◽  
M. Thomas ◽  
C. M. Tsai ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Double Blind ◽  
Equivalent Efficacy ◽  
Secondary Endpoints ◽  
Previously Treated ◽  
Grade 3 ◽  
To Receive

8009 Background: Vandetanib is a once-daily oral inhibitor of VEGFR, EGFR and RET signaling. This phase III study compared the efficacy of vandetanib vs erlotinib in patients (pts) with advanced, previously treated NSCLC. Methods: Eligible pts (stage IIIB/IV NSCLC, PS 0–2, 1–2 prior chemotherapies; all histologies permitted) were randomized 1:1 to receive vandetanib 300 mg/day or erlotinib 150 mg/day until progression/toxicity. The primary objective was to show superiority in progression-free survival (PFS) for vandetanib vs erlotinib. Secondary endpoints included overall survival (OS), objective response rate (ORR), time to deterioration of symptoms (TDS; EORTC QoL Questionnaire) and safety. Results: Between Oct 06-Nov 07, 1240 pts (mean age 61 yrs; 38% female; 22% squamous) were randomized to receive vandetanib (n=623) or erlotinib (n=617). Baseline characteristics were similar in both arms. Median duration of follow-up was 14 months, with 88% pts progressed and 67% dead. There was no difference in PFS for pts treated with vandetanib vs erlotinib (hazard ratio [HR] 0.98, 95.22% CI 0.87–1.10; P=0.721), and no difference in the secondary endpoints of OS (HR 1.01, 95.08% CI 0.89–1.16; P=0.830), ORR (both 12%) and TDS (pain: HR 0.92, P=0.289; dyspnea: HR 1.07, P=0.407; cough: HR 0.94, P=0.455). A preplanned non-inferiority analysis for PFS and OS demonstrated equivalent efficacy for vandetanib and erlotinib. The adverse events (AEs) observed for vandetanib were generally consistent with previous NSCLC studies with vandetanib 300 mg. There was a higher incidence of some AEs (any grade) with vandetanib vs erlotinib, including diarrhea (50% vs 38%) and hypertension (16% vs 2%); rash was more frequent with erlotinib (38% vs 28%). The overall incidence of CTCAE grade ≥3 AEs was also higher with vandetanib (50% vs 40%). The incidence of protocol-defined QTc prolongation in the vandetanib arm was 5%. Conclusions: The study did not meet its primary objective of demonstrating PFS prolongation with vandetanib vs erlotinib in pts with previously treated advanced NSCLC. However, vandetanib and erlotinib showed equivalent efficacy for PFS and OS in a preplanned non-inferiority analysis. [Table: see text]

Results of a phase III, randomized, double-blind, placebo-controlled trial of pegfilgrastim (PEG) in patients (pts) receiving first-line FOLFOX or FOLFIRI and bevacizumab (B) for colorectal cancer (CRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3575-3575
Author(s):  
Tamas Pinter ◽  
Esteban Abella ◽  
Alvydas Cesas ◽  
Adina Croitoru ◽  
Jochen Decaestecker ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Double Blind ◽  
Free Survival ◽  
Clinically Significant ◽  
Grade 3

3575 Background: The literature reports that adding biologics to chemotherapy (ctx) may increase the incidence of clinically significant neutropenia. his trial was conducted to evaluate the efficacy of PEG in reducing the incidence of febrile neutropenia (FN) in pts with locally-advanced (LA) or metastatic (m)CRC receiving first-line treatment with either FOLFOX/B or FOLFIRI/B. Methods: Key eligibility: ≥ 18 years old; measurable, nonresectable CRC per RECIST 1.1. Pts were randomly assigned 1:1 to either placebo or 6 mg PEG ~24 h after ctx/B. The study treatment period included four Q2W cycles, but pts could continue their assigned regimen until progression. Pts were stratified by region (North America vs rest of world), stage (LA vs mCRC), and ctx (FOLFOX vs FOLFIRI). Estimated sample size (N = 800) was based on the expected incidence of grade 3/4 FN (primary endpoint) across the first 4 cycles of ctx/B, powered for PEG superiority over placebo. Other endpoints included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: 845 pts were randomized (Nov 2009 to Jan 2012) and received study treatment; 783 pts completed 4 cycles of ctx/B. Median age was 61 years; 512 (61%) pts were male; 819 (97%) had mCRC; 414 (49%) received FOLFOX, and 431 (51%) received FOLFIRI. Grade 3/4 FN (first 4 cycles) for placebo vs PEG was 5.7% vs 2.4%; OR 0.41; p = 0.014. A similar incidence of other ≥ grade 3 adverse events was seen in both arms (28% placebo; 27% PEG). See table for additional results. Conclusions: PEG significantly reduced the incidence of grade 3/4 FN in this pt population receiving standard ctx/B for CRC. Follow-up is ongoing. Clinical trial information: NCT00911170. [Table: see text]

A phase Ib/IIa study of combination therapy with gemcitabine and Atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 385-385 ◽  
Author(s):  
Beate Schultheis ◽  
Dirk Strumberg ◽  
Jan Kuhlmann ◽  
Martin Wolf ◽  
Karin Link ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Combination Therapy ◽  
Statistical Significance ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Small Patient Number ◽  
The Difference ◽  
Grade 3

385 Background: Atu027 is a liposomally formulated short interfering RNA with anti-metastatic activity, which silences expression of protein kinase N3 (PKN3) in the vascular endothelium. PKN3 acts as a Rho effector downstream of PI3K. This trial was designed to assess safety, pharmacokinetics and efficacy of Atu027 in combination with gemcitabine in advanced pancreatic carcinoma (APC). Methods: 23 patients (pts) with APC stage 3 or 4 were enrolled and randomly assigned to different Atu027 dosing schedules (arm 1: 0.253mg/kg once weekly, n = 11; arm 2: 0.253mg/kg twice-weekly, n = 12) but identical gemcitabine regimen. Response was evaluated according to RECIST 1.1. Quality of life was assessed with EORTC questionnaire QLQ-C30. Results: Combination therapy with Atu027 and gemcitabine was given up to 7.8 months until progression. Grade 3 adverse events (AEs) were reported by 9/11 pts (82%) in arm 1 and 11/12 pts (92%) in arm 2. Grade 4 AEs were reported by two pts in each arm. Interestingly, there was a difference in median progression free survival (mPFS) between the two treatment arms. Arm 1 showed an mPFS of 1.8 [95%CI: 0.4-5.5] months vs. 5.3 [95%CI: 1.5-6.0] months in arm 2, p= 0.399. In a post-hoc analysis of metastatic disease only, the difference in mPFS between the two arms reached statistical significance (1.6 [95%CI:0.4-2.1] vs 2.9 [95%CI:1.0-7.3] months, n = 9 vs 10, p= 0.025). Disease control during treatment was achieved in 4/11 (36%) pts in arm 1 and in 7/12 (58%) pts in arm 2. New lesions occurred in all (6/6) pts in arm 1 who had at least one RECIST re-evaluation but only 5/10 pts (50%) in arm 2. In quality of life analysis, pts in the once-weekly arm showed a stable global health status while pts in the twice-weekly arm reported an improvement (0-100 score change from baseline: -2.3 vs +21.6 after one cycle, N = 7 vs 7). Conclusions: Combination of Atu027 with gemcitabine for the treatment of APC is safe and was well tolerated. Despite the small patient number, there is a clear signal that twice-weekly Atu027 dosing might be superior to the once-weekly regimen. These results suggest efficacy of Atu027 and warrant further investigation with Atu027 added to standard of care in APC. Clinical trial information: NCT01808638.

LOTUS (NCT02162719): A double-blind placebo (PBO)-controlled randomized phase II trial of first-line ipatasertib (IPAT) + paclitaxel (P) for metastatic triple-negative breast cancer (TNBC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1009-1009 ◽  
Author(s):  
Rebecca Alexandra Dent ◽  
Sung-Bae Kim ◽  
Seock-Ah Im ◽  
Marc Espie ◽  
Sibel Blau ◽  
...  
Keyword(s):  
Objective Response ◽  
Locally Advanced ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Akt Inhibitor ◽  
Double Blind ◽  
Common Grade ◽  
Duration Of Response ◽  
Grade 3 ◽  
Median Cumulative Dose

1009 Background: The oral Akt inhibitor IPAT is being evaluated in cancers with a high prevalence of PI3K/Akt pathway activation, including TNBC. Methods: Eligible patients (pts) had measurable inoperable locally advanced/metastatic TNBC previously untreated with systemic therapy. Pts were stratified by prior (neo)adjuvant therapy, chemotherapy-free interval and tumor PTEN status, and randomized 1:1 to P 80 mg/m2 (d1, 8 & 15) with either IPAT 400 mg or PBO (d1–21) q28d until progression or unacceptable toxicity. Co-primary endpoints were progression-free survival (PFS) in the ITT population and pts with PTEN-low tumors by IHC. Secondary endpoints included objective response rate (ORR), duration of response (DoR) and overall survival in the ITT and IHC PTEN-low populations, efficacy in pts with PIK3CA/AKT1/PTEN-altered tumors by next-generation sequencing (NGS), and safety. Results: Baseline characteristics were generally balanced between arms. Efficacy is shown below. The most common grade ≥3 AEs (grouped terms) were diarrhea (23% IPAT+P vs 0% PBO+P; no grade 4 or colitis in either arm), neutropenia (18% vs 8%), asthenia (5% vs 6%), peripheral neuropathy (5% vs 5%) and pneumonia (5% vs 0%). More pts receiving IPAT+P than PBO+P had an AE leading to dose reduction of IPAT/PBO (21% vs 6%) or P (38% vs 11%) but median cumulative dose intensity was similar (IPAT/PBO: 99% vs 100%; P: 100% vs 100%). AEs led to IPAT/PBO discontinuation in 13% vs 11% of pts, respectively; 2 pts (3%) discontinued IPAT for grade 3 diarrhea. Conclusions: Adding IPAT to P for TNBC modestly improved PFS in the ITT pts. The effect was more pronounced in the prespecified subgroup with PIK3CA/AKT1/PTEN alterations, warranting further evaluation of IPAT in these pts. AEs were manageable. Clinical trial information: NCT02162719. [Table: see text]

Results of the JAVELIN Gastric 100 phase 3 trial: avelumab maintenance following first-line (1L) chemotherapy (CTx) vs continuation of CTx for HER2− advanced gastric or gastroesophageal junction cancer (GC/GEJC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 278-278 ◽  
Author(s):  
Markus H. Moehler ◽  
Mikhail Dvorkin ◽  
Mustafa Ozguroglu ◽  
Min-hee Ryu ◽  
Alina Simona Muntean ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Clinical Activity ◽  
Primary Analysis ◽  
Open Label ◽  
Phase 3 ◽  
Post Induction

278 Background: We report the primary analysis of JAVELIN Gastric 100, which compared avelumab (anti–PD-L1) maintenance after 1L CTx vs continued CTx in patients (pts) with GC/GEJC. Methods: In this global, open-label, phase 3 trial (NCT02625610), eligible pts had previously untreated, unresectable, locally advanced/metastatic (LA/M) HER2− GC/GEJC. Pts without progressive disease (PD) after 12 weeks of 1L oxaliplatin/fluoropyrimidine induction were randomized 1:1 to avelumab 10 mg/kg Q2W switch maintenance or continued CTx, stratified by region (Asia vs non-Asia). Primary endpoint was overall survival (OS) post induction in all randomized or PD-L1+ (≥1% of tumor cells, 73-10 assay) pts. Results: 805 pts received induction CTx and 499 pts were randomized (avelumab, n = 249; CTx, n = 250). At data cutoff (Sep 13, 2019), minimum follow-up was 18 months. In the avelumab and CTx arms, median OS post induction/randomization was 10.4 months (95% CI 9.1-12.0) vs 10.9 months (95% CI 9.6-12.4), hazard ratio (HR) 0.91 (95% CI 0.74-1.11; p = 0.1779); 24-month OS rates were 22.1% (95% CI 16.8-28.0) vs 15.5% (95% CI 10.8-20.9), respectively. The HR for OS in PD-L1+ pts (n = 54) was 1.13 (95% CI 0.57-2.23). No OS trend was seen in Asian pts (n = 114; HR 0.90 [95% CI 0.59-1.36]) or other subgroups, except for a potential benefit with avelumab in pts with no metastatic sites at randomization (n = 60; HR 0.52 [95% CI 0.28-0.98]). Progression-free survival was similar between arms (HR 1.04 [95% CI 0.85-1.28]). In the avelumab vs CTx arms, objective response rates (post randomization only) were 13.3% (95% CI 9.3-18.1) vs 14.4% (95% CI 10.3-19.4), and 12-month rates for duration of response were 62.3% (95% CI 40.9-77.9) vs 28.4% (95% CI 13.2-45.7), respectively. Treatment-related adverse event rates (all grades/grade ≥3) were 61.3%/12.8% with avelumab and 77.3%/32.8% with CTx. Conclusions: Avelumab maintenance showed clinical activity and favorable safety vs continued CTx in pts with LA/M GE/GEJC; however, JAVELIN Gastric 100 did not meet its primary objective of demonstrating superior OS in the randomized or PD-L1+ population. Clinical trial information: NCT02625610.

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