First-line (1L) nivolumab (NIVO) plus chemotherapy (chemo) versus chemo in advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): Expanded efficacy and safety data from CheckMate 649.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4002-4002
Author(s):  
Markus H. Moehler ◽  
Kohei Shitara ◽  
Marcelo Garrido ◽  
Pamela Salman ◽  
Lin Shen ◽  
...  
Keyword(s):  
Safety Profile ◽  
Gastroesophageal Junction ◽  
Safety Data ◽  
Progression Free Survival ◽  
Her2 Positive ◽  
Acceptable Safety Profile ◽  
Gastroesophageal Junction Cancer ◽  
Positive Score ◽  
Combined Positive Score ◽  
Grade 3

4002 Background: CheckMate 649 is the largest randomized, global phase 3 study of 1L programmed death (PD)-1 inhibitor–based therapy in GC/GEJC/EAC. 1L NIVO + chemo demonstrated superior overall survival (OS) vs chemo, with progression-free survival (PFS) benefit and an acceptable safety profile in pts whose tumors expressed PD-ligand (L)1 at combined positive score (CPS) ≥ 5 and ≥ 1, and in all randomized pts (Moehler et al. Ann Oncol 2020). We report additional data for all randomized pts. Methods: Eligible pts had previously untreated, unresectable advanced or metastatic GC/GEJC/EAC. Known HER2-positive pts were excluded. Pts were randomized to receive NIVO (360 mg Q3W or 240 mg Q2W) + chemo (XELOX Q3W or FOLFOX Q2W), NIVO + ipilimumab, or chemo. Dual primary endpoints for NIVO + chemo vs chemo were OS and PFS by blinded central review in PD-L1 CPS ≥ 5 pts. Hierarchically tested secondary endpoints were OS in PD-L1 CPS ≥ 1 and all randomized pts. Results: At 12-month minimum follow-up for 1581 randomized pts, NIVO + chemo had a statistically significant OS benefit vs chemo (HR 0.80 [99.3% CI 0.68–0.94; P = 0.0002]) in all randomized pts; PFS benefit was also seen (HR 0.77 [95% CI 0.68–0.87]). OS benefit was observed in multiple prespecified subgroups, consistent with the primary population. Grade 3–4 treatment-related adverse events (TRAEs) were reported in 59% (NIVO + chemo) and 44% (chemo) of pts. TRAEs with potential immunologic etiology (select TRAEs; sTRAEs) are shown in the table. Pts in the NIVO + chemo arm had decreased risk of symptom deterioration on treatment vs those in the chemo arm (HR 0.77 [95% CI 0.63–0.95; P = 0.0129]). Tolerability as measured by the FACT-Ga GP5 item was similar in both treatment groups. Conclusions: The addition of NIVO to chemo demonstrated improved OS and PFS benefit in all randomized pts, along with an acceptable safety profile and maintained tolerability as well as QoL, providing further support for NIVO + chemo as a standard 1L treatment for advanced GC/GEJC/EAC. Clinical trial information: NCT02872116. [Table: see text]

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]

Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study.

2019 ◽  
Vol 37 (18_suppl) ◽  
pp. LBA4007-LBA4007 ◽  
Author(s):  
Josep Tabernero ◽  
Eric Van Cutsem ◽  
Yung-Jue Bang ◽  
Charles S. Fuchs ◽  
Lucjan Wyrwicz ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Final Analysis ◽  
Disease Status ◽  
Phase Iii ◽  
Controlled Study ◽  
Meaningful Improvement ◽  
Primary Endpoints ◽  
Positive Score ◽  
Combined Positive Score ◽  
Grade 3

LBA4007 Background: KEYNOTE062 (NCT02494583) was a randomized, active controlled study of 1L P or P+C vs C in pts with PD-L1 combined positive score ≥1 (CPS ≥1), HER2-negative, advanced GC. Methods: Eligible pts were randomized 1:1:1 to P 200 mg Q3W for up to 2 y, P+C (cisplatin 80 mg/m2 + 5-FU 800 mg/m2/d on d1-d5 Q3W [or capecitabine 1000 mg/m2 BID on d1-d14 Q3W per local guideline]) or placebo Q3W + C. Randomization was stratified by region, disease status, and fluoropyrimidine treatment. Primary endpoints were OS in CPS ≥1 and CPS ≥10 for P+C vs C and P vs C and PFS (RECIST v1.1; central review) in CPS ≥1 for P+C vs C. ORR (RECIST v1.1; central review) in CPS ≥1 for P+C vs C was the secondary endpoint. Final analysis cutoff date was 26 Mar 2019. Results: 763 pts (281 with CPS ≥10) were randomized to P+C (257), P (256), or C (250) (Table). Median follow-up was 11.3 mo. P was noninferior to C for OS in CPS ≥1 per prespecified margins. P vs C prolonged OS in CPS ≥10 (median 17.4 vs 10.8 mo; HR 0.69; 95% CI 0.49-0.97) but wasn’t tested per analysis plan. P+C vs C was not superior for OS in CPS ≥1 or CPS ≥10, with a favorable trend for P+C. P+C did not significantly prolong PFS in CPS ≥1. ORR was higher for P+C vs C. Grade 3-5 drug-related AE rates were 17% (P), 73% (P+C), and 69% (C). Conclusions: As 1L therapy for advanced GC, P was noninferior to C for OS in CPS ≥1 with clinically meaningful improvement for OS in CPS ≥10. P+C did not show superior OS and PFS in CPS ≥1 and OS in CPS ≥10. The safety profile was more favorable for P vs C. Clinical trial information: NCT02494583. [Table: see text]

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]

Trastuzumab (TRA) in combination with different first-line chemotherapies for treatment of HER2-positive metastatic gastric or gastroesophageal junction cancer (MGC): Findings from the German noninterventional observational study HerMES.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4065-4065 ◽  
Author(s):  
Susanna Hegewisch-Becker ◽  
Enno Moorahrend ◽  
Hendrik Kröning ◽  
Volker Petersen ◽  
Carla Hannig ◽  
...  
Keyword(s):  
Observational Study ◽  
Gastroesophageal Junction ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Observation Time ◽  
Phase Iii ◽  
Her2 Positive ◽  
Gastroesophageal Junction Cancer ◽  
Few Data ◽  
Eortc Qlq

4065 Background: The international phase III study ToGA has recently shown that TRA is effective in prolonging survival in HER2-positive MGC. However, few data are available for TRA as part of routine clinical practice. Methods: This non-interventional observational study was conducted to evaluate the efficacy, safety and feasibility of TRA in previously untreated pts with HER2-positive MGC. Results: Between Apr 2010 and Jan 2012, data from 110 pts were collected. All pts were evaluable for safety. Baseline pt characteristics were as follows: median age 63 yrs (range 29–88); gender (male 70%; female 29%); ECOG PS (0: 25%; 1: 50%; 2: 15%; 3: 5%); distant mets (91%); liver mets (54%), lymph node mets (35%); peritoneal carcinomatosis (23%). The median duration of TRA treatment was 4.4 months (0–17.1). According to the schedule of chemotherapy TRA was administered every 2–3 wks in a median dose of 4–6 mg/kg BW. Only 28% of pts received TRA according to the label in combination with cisplatin and 5-FU or capecitabine. The remainder received: cisplatin, 5-FU and leucovorin (17%); 5-FU, leucovorin, oxaliplatin and docetaxel (8%); 5-FU, leucovorin and oxaliplatin (7%); capecitabine (6%); other combinations (25%); TRA monotherapy (7%). Although most pts didn’t receive cisplatin-based therapy, preliminary median progression-free survival was 6.8 months, thus comparable to the ToGA data. Most common adverse events (AEs, all grades) were diarrhoea (7%), vomiting (5%) and nausea (5%). Most common grade 3/4 AEs were vomiting (3%), nausea (2%) and fatigue (2%). Health-related quality of life as assessed by EORTC QLQ-C30 and QLQ-STO22 remained stable during observation time. An updated analysis of approx. 200 pts will be presented at the meeting. Conclusions: TRA combined with diverse chemotherapies is safe and effective in the routine treatment of MGC. Cisplatin-free less toxic regimens are feasible and equally effective. The results are in line with those from the ToGA trial and suggest that treatment with TRA should be regarded as standard of care for pts with HER2-positive MGC.

Melflufen plus dexamethasone (dex) in patients (pts) with relapsed/refractory multiple myeloma (RRMM) exposed/refractory to prior alkylators: A pooled analysis of the O-12-M1 and HORIZON studies.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8048-8048
Author(s):  
Paula Rodríguez-Otero ◽  
Maria-Victoria Mateos ◽  
Albert Oriol ◽  
Alessandra Larocca ◽  
Joan Blade ◽  
...  
Keyword(s):  
Safety Profile ◽  
Alkylating Agents ◽  
Safety Data ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
Study Entry ◽  
Free Survival ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Clinical Trial Information

8048 Background: Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate (PDC) that leverages aminopeptidases and rapidly releases alkylating agents inside tumor cells. Melflufen has a mechanism of action distinct from other alkylating agents (Slipicevic et al. AACR 2020. Abs. 1843). In the O-12-M1 (NCT01897714) and HORIZON (OP-106; NCT02963493) studies, melflufen plus dex showed meaningful efficacy and a clinically manageable safety profile in pts with RRMM (Richardson et al. Lancet Haematol. 2020;7:5; Richardson et al. J Clin Oncol. 2020;Dec 9 [Epub]). This pooled analysis examines pts from these studies exposed to prior alkylators. Methods: Both the O-12-M1 and HORIZON studies included pts with RRMM who received ≥ 2 prior lines of therapy (LoTs) and had a primary endpoint of overall response rate (ORR). Secondary endpoints included progression-free survival (PFS) and safety. Data from the 2 studies were pooled and analyzed according to previous exposure and refractoriness to alkylators before study entry. Refractoriness to prior alkylator therapy was defined as disease that failed to achieve a minimal response or progressed while on therapy, or within 60 d of last therapy. Results: Of 202 pts (HORIZON: n = 157, cutoff January 14, 2020; O-12-M1: n = 45, cutoff October 29, 2019), 178 (88%) had been exposed to alkylators in ≥ 1 prior LoT (see Table for subgroups). Pts exposed and refractory to alkylators in ≥ 2 LoTs had the highest number of pts refractory to an alkylator in the last LoT (61%), and 82% were refractory to an alkylator within 12 mo of study entry. Meaningful response rates were seen in all subgroups, except for pts who were exposed and refractory to alkylators in ≥ 2 prior LoTs (see Table). PFS trended toward being shorter with higher exposure and refractoriness to prior alkylators. Results should be interpreted with caution due to limited pt numbers. Grade 3/4 adverse events (AEs) were similar between pts exposed to prior alkylators (O-12-M1: 85%; HORIZON: 89%) and the overall population (O-12-M1: 84%; HORIZON: 89%). The most common AEs were hematologic, but were mostly reversible and clinically manageable. Nonhematologic AEs were infrequent and primarily grade 1/2. Conclusions: Melflufen in combination with dex showed meaningful efficacy and a clinically manageable safety profile in pts with RRMM exposed/refractory to prior alkylators. Clinical trial information: NCT02963493 and NCT01897714. [Table: see text]

Randomized, Phase II Study of Trastuzumab Beyond Progression in Patients With HER2-Positive Advanced Gastric or Gastroesophageal Junction Cancer: WJOG7112G (T-ACT Study)

2020 ◽  
Vol 38 (17) ◽  
pp. 1919-1927 ◽  
Author(s):  
Akitaka Makiyama ◽  
Yasutaka Sukawa ◽  
Tomomi Kashiwada ◽  
Junji Kawada ◽  
Ayumu Hosokawa ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Growth Factor Receptor ◽  
Dna Amplification ◽  
Progression Free Survival ◽  
First Line ◽  
Her2 Positive ◽  
Gastroesophageal Junction Cancer ◽  
Tumor Tissues ◽  
Secondary Endpoints ◽  
Line Chemotherapy

PURPOSE This study evaluated the continuous use of trastuzumab beyond progression (TBP) in human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastroesophageal junction (G/GEJ) cancer. PATIENTS AND METHODS Patients with HER2-positive advanced G/GEJ cancer refractory to first-line chemotherapy with trastuzumab in combination with fluoropyrimidine and platinum were eligible. Patients were randomly assigned to the paclitaxel (80 mg/m2, days 1, 8, and 15, every 4 weeks) or paclitaxel with trastuzumab (PT; initially 8 mg/kg followed by 6 mg/kg, every 3 weeks) arms. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), response rate, and safety. Biomarkers such as HER2 expression status in tumor tissue after first-line treatment, HER2 amplification evaluated in serum cell-free DNA, and soluble HER2 levels were analyzed. RESULTS Overall, 91 patients were allocated to the paclitaxel (n = 46) and PT (n = 45) arms. The median PFS in the paclitaxel and PT arms was 3.2 and 3.7 months, respectively (hazard ratio [HR], 0.91; 80% CI, 0.67 to 1.22; P = .33), and the median OS in both arms was 10 months (HR, 1.2; 95% CI, 0.75 to 2.0; P = .20). The overall response rates in the paclitaxel and PT arms were 32% and 33%, respectively ( P = 1.00), and safety was comparable between the 2 arms. On exploratory analyses, HER2 positivity of tumor tissues was lost after first-line chemotherapy in 11 (69%) of 16 patients whose tumor tissues were available, and circulating HER2 DNA amplification was detected in 41 (60%) of 68 patients. However, no biomarkers associated with efficacy of TBP were found. CONCLUSION The TBP strategy failed to improve PFS in patients with HER2-positive advanced G/GEJ cancer, and no beneficial biomarkers were found.

KEYNOTE-365 cohort B: Pembrolizumab (pembro) plus docetaxel and prednisone in abiraterone (abi) or enzalutamide (enza)–pretreated patients with metastatic castration-resistant prostate cancer (mCRPC)—New data after an additional 1 year of follow-up.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 10-10
Author(s):  
Leonard Joseph Appleman ◽  
Michael Paul Kolinsky ◽  
William R. Berry ◽  
Margitta Retz ◽  
Loic Mourey ◽  
...  
Keyword(s):  
Oral Prednisone ◽  
Safety Data ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Psa Response ◽  
Positive Score ◽  
Previously Treated ◽  
Combined Positive Score ◽  
Grade 3

10 Background: For men with mCRPC, systemic therapies such as docetaxel and cabazitaxel improve survival, but more effective treatments are needed. KEYNOTE-365 (NCT02861573) is a phase 1b/2 study to examine the safety and efficacy of pembro in combination with 4 different study medications (cohorts A, B, C, D) in mCRPC. Previous data from cohort B with a median of 20 months of follow-up showed that pembro + docetaxel and prednisone was well tolerated and had antitumor activity in patients (pts) with mCRPC previously treated with abi or enza. New efficacy and safety data after an additional year of follow-up are presented. Methods: Cohort B enrolled pts who did not respond to or were intolerant to ≥4 weeks of abi or enza in the prechemotherapy mCRPC state and whose disease progressed within 6 months of screening (determined by PSA progression or radiologic bone/soft tissue progression). Pts received pembro 200 mg IV every 3 weeks (Q3W), docetaxel 75 mg/m2 IV Q3W, and oral prednisone 5 mg twice daily. Primary end points were safety, PSA response rate (PSA decrease >50% from baseline), and ORR per RECIST v1.1 by blinded independent central review. Efficacy and safety were assessed in all pts as treated. Results: Of the 104 treated pts, median age was 68.0 years (range, 50-86), 23.1% had PD-L1–positive tumors (combined positive score ≥1), 25.0% had visceral disease, and 50.0% had measurable disease. Median time from enrollment to data cutoff was 32.4 months (range 13.9-40.3); 101 pts discontinued, primarily because of disease progression (77.9%). Efficacy outcomes are reported in the table below. Treatment-related adverse events (TRAEs) occurred in 100 pts (96.2%); the most frequent (≥30%) were diarrhea (41.3%), fatigue (41.3%), and alopecia (40.4%). Grade 3-5 TRAEs occurred in 46 pts (44.2%). Five pts (4.8%) died of AEs; 2 were treatment-related pneumonitis. Conclusions: After another year of follow-up, pembro + docetaxel and prednisone showed improved ORR and PSA response rates compared to the prior dataset in pts with mCRPC previously treated with abi or enza. Safety was consistent with known profiles of each agent and will be further evaluated in a phase 3 study (KEYNOTE-921). Clinical trial information: NCT02861573. [Table: see text]

The impact of prior therapies on outcomes with trifluridine/tipiracil (FTD/TPI) in the phase III TAGS trial.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 247-247
Author(s):  
Kohei Shitara ◽  
Ben George ◽  
Julien Taieb ◽  
Raghav Sundar ◽  
Marwan Fakih ◽  
...  
Keyword(s):  
Safety Profile ◽  
Gastroesophageal Junction ◽  
Progression Free Survival ◽  
Prior Treatment ◽  
Phase Iii ◽  
Phase 3 ◽  
Gastroesophageal Junction Cancer ◽  
Third Line ◽  
Post Hoc ◽  
The Impact

247 Background: It is unclear whether prior treatment with ramucirumab (RAM) or RAM plus paclitaxel (PAC), standard second-line treatments for metastatic gastric or gastroesophageal junction cancer (mGC/GEJC), can influence outcomes with third-line chemotherapy in this patient (pt) population (pop). In the phase 3 TAGS trial, FTD/TPI showed a survival benefit vs placebo (PBO) in pts with mGC/GEJC who had received ≥2 prior chemotherapy regimens. Post hoc analyses were performed to assess the impact of prior RAM, PAC or RAM+PAC treatment on the efficacy and safety of FTD/TPI in TAGS. Methods: Pts in the TAGS trial were categorized into 5 subgroups based on prior treatment received as follows: A) RAM (alone or combined with other agents), B) no RAM, C) PAC (but no RAM), D) RAM+PAC (sequentially or in combination) and E) neither PAC nor RAM. While subgroups A and B were prespecified, all other subgroups were identified post hoc. Efficacy (overall survival [OS] and progression-free survival [PFS]) and safety were assessed in these subgroups. Results: In the overall pop (N=507), 33% had received prior RAM (alone/combined); 30% prior RAM+PAC; 27% prior PAC but no RAM; and 40% had received neither PAC nor RAM. As only 3% of all pts received prior RAM but no PAC, that subgroup was not considered in this analysis. FTD/TPI treatment was consistently associated with benefits in OS and PFS vs placebo across all pt subgroups (Table). Among pts randomized to FTD/TPI, OS benefit was similar between pts who received RAM+PAC vs those who received neither (HR, 1.15; 95% CI, 0.84–1.58) and between pts who received PAC (but no RAM) vs those who received neither (HR, 0.91; 95% CI, 0.66–1.25). The FTD/TPI safety profile was consistent across all subgroups, with similar overall incidences of grade ≥3 adverse events (AEs). Minor variations in hematologic toxicities were noted (Table). Conclusions: In the phase 3 TAGS trial, FTD/TPI treatment in the third or later line provided efficacy benefits vs PBO and demonstrated a consistent safety profile in pts with mGC/GEJC regardless of prior treatments. Clinical trial information: NCT02500043. [Table: see text]

scholarly journals Pertuzumab plus trastuzumab and chemotherapy for Japanese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer: a subgroup analysis of the JACOB trial

2019 ◽  
Vol 25 (2) ◽  
pp. 301-311
Author(s):  
Kohei Shitara ◽  
Hiroki Hara ◽  
Takaki Yoshikawa ◽  
Kazumasa Fujitani ◽  
Tomohiro Nishina ◽  
...  
Keyword(s):  
Adverse Events ◽  
Subgroup Analysis ◽  
Gastroesophageal Junction ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Phase Iii ◽  
Her2 Positive ◽  
Serious Adverse Events ◽  
Gastroesophageal Junction Cancer

Abstract Background The phase III JACOB trial (NCT01774786) compared the efficacy and safety of pertuzumab and trastuzumab plus chemotherapy with placebo and trastuzumab plus chemotherapy in patients with previously untreated human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric or gastroesophageal junction cancer. We conducted a subgroup analysis in Japanese patients. Methods Patients were randomized 1:1 to pertuzumab 840 mg or placebo, plus trastuzumab (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) and chemotherapy (cisplatin 80 mg/m2, and capecitabine 1000 mg/m2 twice daily for 28 doses or 5-fluorouracil 800 mg/m2 every 24 h for 120 h), every 3 weeks. Continuation of chemotherapy after 6 cycles was at the discretion of the patient and the treating physician. Results A total of 40 Japanese patients were included in each arm. Median overall survival was 22.0 months (95% confidence interval [CI] 13.8–not evaluable) and 15.6 months (95% CI 9.7–19.2) in the pertuzumab and placebo arms, respectively (hazard ratio [HR] 0.64 [95% CI 0.37–1.10]). Median progression-free survival was 12.4 months (95% CI 6.1–14.1) in the pertuzumab arm and 6.3 months (95% CI 4.3–8.1) in the placebo arm (HR 0.50 [95% CI 0.30–0.82]). Grade ≥ 3 adverse events and serious adverse events were more frequent in the pertuzumab arm than the placebo arm. Conclusions Results from this subgroup analysis of the JACOB trial suggest similar efficacy of pertuzumab in Japanese patients and patients in the overall population, encouraging continued investigation of new agents for gastric cancer in Japanese patients.

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