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]

KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1000-1000 ◽  
Author(s):  
Javier Cortes ◽  
David W. Cescon ◽  
Hope S. Rugo ◽  
Zbigniew Nowecki ◽  
Seock-Ah Im ◽  
...  
Keyword(s):  
Cox Regression ◽  
Phase Iii ◽  
Double Blind ◽  
Meaningful Improvement ◽  
Kaplan Meier ◽  
Primary Endpoints ◽  
Immune Mediated ◽  
Locally Recurrent ◽  
Grade 3

1000 Background: Pembrolizumab (pembro) monotherapy showed promising antitumor activity and manageable safety in patients (pts) with metastatic TNBC in KEYNOTE-012, -086 and -119. KEYNOTE-355 (ClinicalTrials.gov, NCT02819518) compared pembro + chemotherapy (chemo) vs placebo (pbo) + chemo for previously untreated locally recurrent inoperable or metastatic TNBC. Methods: Pts with ≥6 mo DFI were randomized 2:1 to pembro + chemo (nab-paclitaxel; paclitaxel; or gemcitabine/carboplatin) or pbo + chemo for up to 35 administrations of pembro/pbo or until progression/intolerable toxicity. Pts were stratified by chemo type (taxane vs gemcitabine/carboplatin), PD-L1 status (CPS ≥1 vs <1), and prior (neo)adjuvant treatment with same-class chemo (yes vs no). Dual primary endpoints are PFS (RECIST v1.1, blinded independent central review) and OS by tumor PD-L1 expression (CPS ≥10 and ≥1) and in all pts. PFS was estimated using the Kaplan-Meier method. Stratified log-rank tests were used to assess treatment group differences. HR and 95% CIs were based on a stratified Cox regression model. AEs were monitored throughout the study and graded per NCI CTCAE v4.0. Results: As of Dec 11 2019, median follow-up was 17.5 mo for pembro + chemo (n=566) and 15.5 mo for chemo (n=281). Pembro + chemo significantly improved PFS vs chemo alone in pts with CPS ≥10 tumors (Table), meeting one of the protocol-defined primary objectives. Although the boundary for a statistically significant benefit of pembro + chemo in pts with CPS ≥1 tumors was not met and formal testing in ITT was not performed, the pembro treatment effect increased with PD-L1 enrichment (Table). OS follow-up is ongoing. Grade 3-5 treatment-related AE rates were 68.1% with pembro + chemo (2 deaths) vs 66.9% with chemo (0 deaths); rates of grade 3-4 immune-mediated AEs and infusion reactions were 5.5% vs 0%. Clinical trial information: NCT02819518 . Conclusion: Pembro combined with several chemo partners showed a statistically significant and clinically meaningful improvement in PFS vs chemo alone in pts with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1 (CPS ≥10). Pembro + chemo was generally well tolerated, with no new safety concerns. [Table: see text]

Final analysis of KEYNOTE-189: Pemetrexed-platinum chemotherapy (chemo) with or without pembrolizumab (pembro) in patients (pts) with previously untreated metastatic nonsquamous non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9582-9582
Author(s):  
Delvys Rodriguez-Abreu ◽  
Steven Francis Powell ◽  
Maximilian Hochmair ◽  
Shirish M. Gadgeel ◽  
Emilio Esteban ◽  
...  
Keyword(s):  
Final Analysis ◽  
Phase Iii ◽  
First Line ◽  
Primary Endpoints ◽  
Improved Outcomes ◽  
Grade 3 ◽  
Platinum Chemotherapy ◽  
To Receive ◽  
Clinical Trial Information ◽  
Nonsquamous Nsclc

9582 Background: The phase III KEYNOTE-189 study (NCT02578680), showed significant improvements in OS and PFS with pembro + chemo vs placebo + chemo in pts with previously untreated metastatic nonsquamous NSCLC without sensitizing EGFR/ALK mutations. We report the protocol-specified final analysis of KEYNOTE-189. Methods: Pts were randomized 2:1 to receive 35 cycles of pembro 200 mg Q3W (n = 410) or placebo Q3W (n = 206) plus 4 cycles of pemetrexed (pem) and carboplatin/cisplatin followed by maintenance pem. Pts in the placebo + chemo arm could crossover to pembro upon PD. PFS and OS were primary endpoints; ORR was a secondary endpoint. PFS2 (time from randomization to objective tumor progression on next-line treatment/death), was an exploratory endpoint. Results: At data cutoff (May 20, 2019), median (range) time from randomization to data cutoff was 31.0 (26.5–38.8) mo. 17 pts in the pembro + chemo arm and 1 pt in the placebo + chemo arm were receiving initially assigned treatment; 84 pts crossed over to pembro. Median (95% CI) OS (22.0 [19.5–24.5] vs 10.6 [8.7–13.6] mo; HR 0.56 [95% CI, 0.46–0.69]) and PFS (9.0 [8.1–10.4] vs 4.9 [4.7–5.5] mo; HR 0.49 [95% CI, 0.41–0.59]) were longer with pembro + chemo vs placebo + chemo (Table). The 2-y OS rate was 45.7% vs 27.3% and the 2-y PFS rate was 22.0% vs 3.4%. ORR was 48.3% with pembro + chemo vs 19.9% with placebo + chemo. 56 pts in the pembro + chemo arm completed 35 cycles of pembro among whom ORR was 85.7% (4 CR, 44 PR, 8 SD) and median OS was not reached. 292 (72.1%) pts in the pembro + chemo arm and 135 (66.8%) pts in the placebo + chemo arm had grade 3–5 AEs. Conclusions: Pembro + chemo continued to show improved outcomes in OS, PFS, ORR and PFS2 compared with placebo + chemo, with manageable toxicity. These findings support first-line pembro + chemo in pts with previously untreated metastatic nonsquamous NSCLC. Clinical trial information: NCT02578680 . [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]

Phase 2 study of pembrolizumab (pembro) monotherapy for previously treated metastatic triple-negative breast cancer (mTNBC): KEYNOTE-086 cohort A.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1008-1008 ◽  
Author(s):  
Sylvia Adams ◽  
Peter Schmid ◽  
Hope S. Rugo ◽  
Eric P. Winer ◽  
Delphine Loirat ◽  
...  
Keyword(s):  
Primary Endpoints ◽  
Phase 2 Study ◽  
Heavily Pretreated ◽  
Secondary Endpoints ◽  
Positive Score ◽  
Previously Treated ◽  
Combined Positive Score ◽  
Grade 3 ◽  
Ecog Ps

1008 Background: In KEYNOTE-012, pembro showed durable activity and manageable safety in patients (pts) with PD-L1+ mTNBC. Cohort A of KEYNOTE-086 (NCT02447003) examined the efficacy/safety of pembro in previously treated mTNBC, regardless of PD-L1 expression. Methods: Pts with centrally confirmed mTNBC, ≥1 prior chemotherapy for metastatic disease, and ECOG PS 0-1 had pembro 200 mg Q3W for up to 24 mo; imaging q 9 wk for the first 12 mo, then q 12 wk. Clinically stable pts with PD could remain on pembro until PD confirmed on next assessment. Primary endpoints: ORR (RECIST v1.1, central review) in all pts and pts with PD-L1+ tumors, and safety. Secondary endpoints: DOR, disease control rate (DCR; CR + PR + SD ≥24 wk), PFS, and OS. Planned enrollment was 160 pts; analysis based on data as of Nov 10, 2016. Results: 60% of screened PD-L1-evaluable pts had PD-L1+ tumors (combined positive score ≥1%). Of 170 pts enrolled (100% women; median age 54 y), 44% had ≥3 prior lines of therapy, 51% had elevated LDH, 74% had visceral mets and 62% had PD-L1+ tumors. After a median follow-up of 10.9 mo, 9 (5%) pts remained on pembro. Treatment-related AEs (TRAEs) of any grade and grade 3-4 occurred in 60% and 12% of pts, respectively; 4% discontinued due to TRAEs. There were no deaths due to AE. Overall ORR was 5% regardless of PD-L1 expression (Table). Best overall response was 0.6% CR, 4% PR, 21% SD; not evaluable (3%). DCR was 8% (95% CI 4-13). Median DOR was 6.3 mo (range 1.2+ to 10.3+); 5 (63%) responders w/o PD at data cutoff. Median PFS and OS were 2.0 mo (95% CI 1.9-2.0) and 8.9 mo (95% CI 7.2-11.2), with 6-mo rates of 12% and 69%, respectively. ORR was numerically lower in pts with poor prognostic factors (e.g., high LDH, liver/visceral mets; Table). Conclusions: In KEYNOTE-086 Cohort A, pembro monotherapy showed manageable safety and durable responses in a subset of pts with heavily pretreated mTNBC. Randomized studies of monotherapy and combination therapy are ongoing. Clinical trial information: NCT02447003. [Table: see text]

SWOG S1216: A phase III randomized trial comparing androgen deprivation therapy (ADT) plus TAK-700 with ADT plus bicalutamide in patients (pts) with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) (NCT01809691).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5001-5001
Author(s):  
Neeraj Agarwal ◽  
Catherine Tangen ◽  
Maha H. A. Hussain ◽  
Shilpa Gupta ◽  
Melissa Plets ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Performance Status ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Meaningful Improvement ◽  
Intention To Treat ◽  
Grade 3

5001 Background: Tak is an oral selective nonsteroidal 17, 20-lyase inhibitor that blocks the synthesis of gonadal and adrenal androgens. We evaluated the clinical benefit of Tak with ADT in pts with newly diagnosed mHSPC. Methods: Pts with mHSPC with a Zubrod performance status (PS) of 0-2 and a PSA of ≥ 2 ng/ml were randomized 1:1 to ADT+Tak (300 mg twice daily) or ADT+Bic (50 mg daily). Stratification factors included PS (0-1 vs ≥2), extent of disease (minimal vs extensive), and receipt of ADT prior to registration (yes vs no). The primary endpoint was overall survival (OS). Secondary endpoints were progression free survival (PFS; based on PSA, imaging or clinical progression), PSA at 7 months (≤0.2 vs 0.2 < PSA; ≤-4 vs. > 4 ng/ml) and adverse event (AE) profile. With 2.75 yrs to accrue 1,186 eligible pts and 3 additional yrs of follow-up, we would have 90% power to determine a 33% improvement in OS from 54 to 72 mos (1-sided α = 0.025). A final analysis was pre-specified after 523 deaths using a 1-sided α = 0.022 to account for interim analyses. Results: Between 3/2013 and 7/2017, 1,313 pts were randomized and 1,279 were included in the intention-to-treat (ITT) analysis (32 pts were ineligible and 2 pts withdrew consent). Median age was 68 yrs and 10% of subjects were Black. Median PSA was 30 ng/mL (range 2-6710) and 49% of pts had extensive disease. After a median follow-up of 4.9 yrs, PFS and PSA response were significantly improved with Tak over Bic but no significant improvement in OS was observed (Table). More grade 3/4 AEs occurred in Tak vs. Bic arms (43% vs. 14%), and included hypertension (20% vs. 5%) and fatigue (5% vs. 2%). Five pts in Tak and 1 pt in the Bic arm had grade 5 AE. Conclusions: Despite clinically meaningful improvement in various outcome measures with Tak+ADT over Bic+ADT in this representative population of mHSPC, the improvement in OS did not meet the pre-specified criteria for statistical significance. The median OS of 70 mos in the control arm (standard ADT) was higher than that reported in contemporary phase 3 trials in this setting, and 16 mos higher than originally estimated. This trial sets a new landmark for survival estimates when pts with mHSPC have access to multiple approved subsequent life-prolonging therapies. Funding: NIH/NCI/NCTN grants U10CA180888, U10CA180819, U10CA180820; U10CA180821; and in part by Millennium Pharmaceuticals, Inc. (Takeda Pharmaceutical Company LTD) Clinical trial information: NCT01809691. [Table: see text]

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]

1L pembrolizumab (pembro) versus chemotherapy (chemo) for choice-of-carboplatin patients with advanced urothelial carcinoma (UC) in KEYNOTE-361.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 450-450
Author(s):  
Thomas Powles ◽  
Tibor Csőszi ◽  
Mustafa Ozguroglu ◽  
Nobuaki Matsubara ◽  
Lajos Geczi ◽  
...  
Keyword(s):  
The United States ◽  
Risk Difference ◽  
Phase Iii ◽  
Study Cohort ◽  
Full Study ◽  
Dose Study ◽  
Positive Score ◽  
Combined Positive Score ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3

450 Background: 1L pembro is approved in advanced UC for cisplatin-ineligible pts with PD-L1 combined positive score (CPS) ≥10 and any platinum-ineligible pts regardless of CPS in the United States based on single-arm trial data. In the phase III KEYNOTE-361 study, 1L pembro + chemo did not statistically significantly improve PFS or OS vs chemo for pts with advanced UC; formal testing of 1L pembro vs chemo was not performed. We present an exploratory analysis of outcomes with pembro vs chemo for choice-of-carboplatin (carbo) pts in KEYNOTE-361 (NCT02853305). Methods: At randomization, choice of platinum agent (cisplatin or carbo) plus gemcitabine for each pt was selected based on investigator’s assessment of cisplatin ineligibility. ORR/DOR per RECIST v1.1 by blinded independent central review and OS were determined for all pts selected for carbo (“choice-of-carbo”) and also choice-of-carbo pts with CPS ≥10. Risk difference assessment for select AEs for pembro vs chemo was conducted in choice-of-carbo pts who received ≥1 dose study treatment. Results: As of Apr 29, 2020, the median (range) time from randomization to data cutoff in the full study cohort was 31.7 (22.0-42.3) mo. At randomization, renal impairment was the most common reason for choice of carbo by investigators (36% of all pts). 170 choice-of-carbo pts were randomized to the pembro arm, and 196 choice-of-carbo pts to the chemo arm. Median OS in this subgroup was 14.6 mo with pembro vs 12.3 mo with chemo (HR 0.83 [95% CI 0.65-1.06]). 18-mo OS rate was 42% with pembro vs 40% with chemo. ORR to pembro vs chemo was 27.6% vs 41.8%. Median (range) DOR with pembro vs chemo was not reached (NR) (3.2+-36.1+ mo) vs 6.3 (1.8+-33.8+) mo. 84/170 (49%) and 89/196 (45%) choice-of-carbo pts in the pembro and chemo arms, respectively, had CPS ≥10. In this subgroup, median OS was 15.6 mo with pembro vs 13.5 mo with chemo (HR 0.82 [95% CI 0.57-1.17]). 18-mo OS rate was 44% with pembro vs 43% with chemo. ORR to pembro vs chemo was 29.8% vs 46.1%. Median (range) DOR with pembro vs chemo was NR (4.2-36.1+ mo) vs 8.3 (2.1+-33.8+) mo. Among treated pts (N=166 for pembro, N=190 for chemo), 112 pts (68%) in the pembro arm and 163 pts (86%) in the chemo arm had grade 3-5 AEs of any cause. Pembro was associated with a higher risk of pruritus, while chemo was associated with a higher risk of decreased white blood cell, neutrophil, and platelet counts, nausea, thrombocytopenia, neutropenia, and anemia. Conclusions: Due to the trial design, this subset was not statistically tested and is exploratory. Median OS and 18-mo OS rates did not appear markedly different in the two arms; some parameters such as DOR favored pembro, although longer follow-up is needed to determine median DOR for pembro. The PD-L1 CPS ≥10 did not clearly enrich for responders to pembro in choice-of-carbo pts. Pembro was associated with a lower rate of grade 3-5 AEs of any cause than chemo. Clinical trial information: NCT02853305.

KEYNOTE-059 cohort 1: Pembrolizumab (Pembro) monotherapy in previously treated advanced gastric or gastroesophageal junction (G/GEJ) cancer in patients (Pts) with PD-L1+ tumors—Asian subgroup analysis.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 723-723
Author(s):  
Kei Muro ◽  
Charles S. Fuchs ◽  
Raymond Woo-Jun Jang ◽  
Taroh Satoh ◽  
Manuela Machado ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Prior Therapy ◽  
Phase 2 Study ◽  
The Us ◽  
Positive Score ◽  
Previously Treated ◽  
Combined Positive Score ◽  
Us Fda ◽  
Grade 3

723 Background: The US FDA approved pembro for treating pts with 1) recurrent locally advanced or metastatic G/GEJ adenocarcinoma, whose disease has progressed on or after ≥2 prior therapies and whose tumors express PD-L1 (combined positive score [CPS] ≥1), and 2) unresectable or metastatic, microsatellite instability-high (MSI-H) solid tumors that have progressed after prior therapy and who have no fitting options. We report Asian subgroup analyses from cohort 1 of KEYNOTE-059 (NCT02335411), a global, phase 2 study in advanced G/GEJ cancer. Methods: Eligible pts had measurable recurrent or metastatic G/GEJ adenocarcinoma whose disease has progressed on ≥2 prior chemotherapy regimens. Pts received pembro 200 mg Q3W up to 2 y. PD-L1+ tumors had a CPS ≥1. Primary end points were ORR (RECIST 1.1, by central review) and safety. Results: Cohort 1 enrolled 259 pts; 57% had PD-L1+ tumors. MSI status was evaluable in 174 tumor samples; of these, 7 were MSI-H. At data cutoff (4/21/2017), median (range) follow-up was 6 mo (1-25). Overall ORR was 12% (95% CI, 8-17) and median (range) DOR was 14 mo (2-19+). PFS6-mo rate was 15% and OS6-mo rate was 46%. In pts with PD-L1+ tumors, ORR was 16% (95% CI, 11-23) and median (range) DOR was 14 mo (3+-19+). In pts with PD-L1+ tumors, PFS6-mo rate was 20% and OS6-mo rate was 50%. In pts with MSI-H tumors, ORR was 57% (95% CI, 18-90) and median (range) DOR was not reached (5-14+ mo). In cohort 1, 41 pts were Asian and 218 pts were non-Asian. PD-L1+ tumors occurred in 42% of Asian pts and 60% of non-Asian pts. ORR was 12% (95% CI, 2-36) in Asian pts with PD-L1+ tumors and 17% (95% CI, 11-24) in non-Asian pts with PD-L1+ tumors. One of 7 pts with MSI-H tumors was Asian; this pt had CR. Grade 3-5 treatment-related AEs occurred in 17% and 18% of Asian and non-Asian pts, similar to the overall cohort. Conclusions: Pembro showed durable clinical benefit in previously treated pts with advanced G/GEJ cancer, especially those with PD-L1+ or MSI-H tumors. Safety and efficacy were similar in Asian and non-Asian pts. These findings highlight pembro as a standard treatment option in Asian and non-Asian pts with advanced G/GEJ cancer. Clinical trial information: NCT02335411.

scholarly journals Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial

2021 ◽  
Author(s):  
Charles S. Fuchs ◽  
Mustafa Özgüroğlu ◽  
Yung-Jue Bang ◽  
Maria Di Bartolomeo ◽  
Mario Mandala ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Standard Dose ◽  
Gastroesophageal Junction ◽  
Cox Proportional Hazards ◽  
Phase 3 ◽  
Gastroesophageal Junction Cancer ◽  
Cox Proportional Hazards Models ◽  
Primary Endpoints ◽  
Positive Score ◽  
Combined Positive Score

Abstract Background In the phase 3 KEYNOTE-061 study (cutoff: 10/26/2017), pembrolizumab did not significantly prolong OS vs paclitaxel as second-line (2L) therapy in PD-L1 combined positive score (CPS) ≥ 1 gastric/GEJ cancer. We present results in CPS ≥ 1, ≥ 5, and ≥ 10 populations after two additional years of follow-up (cutoff: 10/07/2019). Methods Patients were randomly allocated 1:1 to pembrolizumab 200 mg Q3W for ≤ 35 cycles or standard-dose paclitaxel. Primary endpoints: OS and PFS (CPS ≥ 1 population). HRs were calculated using stratified Cox proportional hazards models. Results 366/395 patients (92.7%) with CPS ≥ 1 died. Pembrolizumab demonstrated a trend toward improved OS vs paclitaxel in the CPS ≥ 1 population (HR, 0.81); 24-month OS rates: 19.9% vs 8.5%. Pembrolizumab incrementally increased the OS benefit with PD-L1 enrichment (CPS ≥ 5: HR, 0.72, 24-month rate, 24.2% vs 8.8%; CPS ≥ 10: 0.69, 24-month rate, 32.1% vs 10.9%). There was no difference in median PFS among treatment groups (CPS ≥ 1: HR, 1.25; CPS ≥ 5: 0.98; CPS ≥ 10: 0.79). ORR (pembrolizumab vs paclitaxel) was 16.3% vs 13.6% (CPS ≥ 1), 20.0% vs 14.3% (CPS ≥ 5), and 24.5% vs 9.1% (CPS ≥ 10); median DOR was 19.1 months vs 5.2, 32.7 vs 4.8, and NR vs 6.9, respectively. Fewer treatment-related AEs (TRAEs) occurred with pembrolizumab than paclitaxel (53% vs 84%). Conclusion In this long-term analysis, 2L pembrolizumab did not significantly improve OS but was associated with higher 24-month OS rates than paclitaxel. Pembrolizumab also increased OS benefit with PD-L1 enrichment among patients with PD-L1-positive gastric/GEJ cancer and led to fewer TRAEs than paclitaxel. Trial registration ClinicalTrials.gov, NCT02370498

Checkmate 577:Health-related quality of life (HRQoL) in a randomized, double-blind phase III study of nivolumab (NIVO) versus placebo (PBO) as adjuvant treatment in patients (pts) with resected esophageal or gastroesophageal junction cancer (EC/GEJC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 167-167
Author(s):  
Eric Van Cutsem ◽  
Prianka Singh ◽  
James M. Cleary ◽  
Ronan Joseph Kelly ◽  
Markus H. Moehler ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Visual Analogue Scale ◽  
Repeated Measures ◽  
Analogue Scale ◽  
Gastroesophageal Junction ◽  
Neoadjuvant Chemoradiotherapy ◽  
Phase Iii ◽  
Meaningful Improvement ◽  
Utility Index ◽  
Patient Reported

167 Background: NIVO is the first adjuvant therapy to provide a statistically significant and clinically meaningful improvement in disease-free survival (DFS) versus PBO in resected EC/GEJC following neoadjuvant chemoradiotherapy as demonstrated by CheckMate 577. NIVO was well tolerated with an acceptable safety profile. This analysis provides additional information on the exploratory HRQoL endpoints in this clinical trial. Methods: The effect of NIVO versus PBO on HRQoL, including general and disease-related symptoms, functioning, disease burden, and overall QoL, was assessed using FACT-E and EQ-5D-3L patient-reported outcome (PRO) questionnaires administered at baseline (BL), every 4 weeks during the 12-month treatment period, and at post-treatment follow-up visits (up to 2 years after last dose). Longitudinal change from BL in PRO scores over 12 months was assessed using descriptive statistics. Additionally, mixed model for repeated measures and time to deterioration analyses evaluated the difference between treatment with NIVO and PBO (data not shown). Results: 794 pts with EC/GEJC were randomized 2:1 to NIVO (n = 532) or PBO (n = 262). PRO completion rates were ≥ 95% at BL and ~ 90% at 12 months on treatment. Mean (SD) BL HRQoL scores were similar between treatment arms for the FACT-E total score (NIVO: 133.40 [20.97]; PBO: 134.03 [20.40]); esophageal cancer subscale (ECS; NIVO: 50.2 [9.3]; PBO: 50.1 [8.9]); EQ-5D Visual Analogue Scale (NIVO: 70.4 [22.3]; PBO: 69.1 [24.1]); and EQ-5D Utility Index (NIVO: 0.820 [0.179]; PBO: 0.831 [0.163]) based on the UK value set. Descriptive analyses showed a trend for increases from baseline at most time points through week 49 for both NIVO and PBO treatment groups for FACT-E total score, ECS, and EQ-5D Visual Analogue Scale and Utility Index. Conclusions: Preliminary results from CheckMate 577 demonstrated that pts on NIVO treatment showed trends of improvement in both esophageal-specific and general HRQoL. Similar trends were also observed in pts treated with PBO over 1 year. Pts treated with NIVO did not experience a reduction in HRQoL, further supporting clinical data to demonstrate treatment benefit and tolerability for adjuvant NIVO in pts with resected EC/GEJC. Clinical trial information: NCT02743494.

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