scholarly journals RACE-trial: neoadjuvant radiochemotherapy versus chemotherapy for patients with locally advanced, potentially resectable adenocarcinoma of the gastroesophageal junction - a randomized phase III joint study of the AIO, ARO and DGAV

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Sylvie Lorenzen ◽  
Alexander Biederstädt ◽  
Ulrich Ronellenfitsch ◽  
Christoph Reißfelder ◽  
Stefan Mönig ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Preoperative Chemotherapy ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Neoadjuvant Radiochemotherapy ◽  
Perioperative Chemotherapy ◽  
Free Survival ◽  
Link Type

Abstract Background Despite obvious advances over the last decades, locally advanced adenocarcinomas of the gastroesophageal junction (GEJ) still carry a dismal prognosis with overall 5-year survival rates of less than 50% even when using modern optimized treatment protocols such as perioperative chemotherapy based on the FLOT regimen or radiochemotherapy. Therefore the question remains whether neoadjuvant chemotherapy or neoadjuvant radiochemotherapy is eliciting the best results in patients with GEJ cancer. Hence, an adequately powered multicentre trial comparing both therapeutic strategies is clearly warranted. Methods The RACE trial is a an investigator initiated multicenter, prospective, randomized, stratified phase III clinical trial and seeks to investigate the role of preoperative induction chemotherapy (2 cycles of FLOT: 5-FU, leucovorin, oxaliplatin, docetaxel) with subsequent preoperative radiochemotherapy (oxaliplatin weekly, 5-FU plus concurrent fractioned radiotherapy to a dose of 45 Gy) compared to preoperative chemotherapy alone (4 cycles of FLOT), both followed by resection and postoperative completion of chemotherapy (4 cycles of FLOT), in the treatment of locally advanced, potentially resectable adenocarcinoma of the gastroesophageal junction. Patients with cT3–4, any N, M0 or cT2 N+, M0 adenocarcinoma of the GEJ are eligible for inclusion. The RACE trial aims to enrol 340 patients to be allocated to both treatment arms in a 1:1 ratio stratified by tumour site. The primary endpoint of the trial is progression-free survival assessed with follow-up of maximum 60 months. Secondary endpoints include overall survival, R0 resection rate, number of harvested lymph nodes, site of tumour relapse, perioperative morbidity and mortality, safety and toxicity and quality of life. Discussion The RACE trial compares induction chemotherapy with FLOT followed by preoperative oxaliplatin and 5-Fluorouracil-based chemoradiation versus preoperative chemotherapy with FLOT alone, both followed by surgery and postoperative completion of FLOT chemotherapy in the treatment of locally advanced, non-metastatic adenocarcinoma of the GEJ. The trial aims to show superiority of the combined chemotherapy/radiochemotherapy treatment, assessed by progression-free survival, over perioperative chemotherapy alone. Trial registration ClinicalTrials.gov; NCT04375605; Registered 4th May 2020;

Delta-volume radiomics of induction chemotherapy to predict outcome of subsequent chemoradiotherapy for locally advanced hypopharyngeal cancer

2021 ◽  
pp. 030089162110390
Author(s):  
Che-Wei Su ◽  
Jehn-Chuan Lee ◽  
Yi-Fang Chang ◽  
Nai-Wen Su ◽  
Pei-Hsuan Lee ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Concurrent Chemoradiotherapy ◽  
Locally Advanced ◽  
Area Under The Curve ◽  
Progression Free Survival ◽  
Hypopharyngeal Cancer ◽  
Imaging Biomarker ◽  
Free Survival ◽  
Before And After ◽  
Selection Operator

Introduction: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is recommended for larynx-preserving treatment of locally advanced hypopharyngeal cancer (LAHC). However, the conventional evaluation of response is not robust enough to predict the outcome of subsequent treatments. This study aimed to develop an imaging biomarker using changes in radiomic features in invasive tumor front (ITF) by IC to predict treatment outcome of subsequent CCRT in LAHC. Methods: From 2006 to 2018, 59 computed tomography (CT) scan images before and after IC in patients with LAHC were used to contour the gross tumor volumes (GTVs). A total of 48 delta-volume radiomics features were acquired from the absolute spatial difference of GTVs (delta-GTV) before and after IC, conceptually representing a consistent portion of ITF. Least absolute shrinkage and selection operator regression (LASSO) was used to select features for establishing the model generating radiomic score (R score). Results: A model including 5 radiomic features from delta-GTV to predict better progression-free survival (PFS) of patients receiving subsequent CCRT was established. The R score was validated with all datasets (area under the curve 0.77). Low R score (<–0.16) was associated with improved PFS ( p < 0.05). Conclusions: The established radiomic model for ITF from radiomic features of delta-GTV after IC might be a potential imaging biomarker for predicting clinical outcome of subsequent CCRT in LAHC.

scholarly journals CheckMate-032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients With Metastatic Esophagogastric Cancer

2018 ◽  
Vol 36 (28) ◽  
pp. 2836-2844 ◽  
Author(s):  
Yelena Y. Janjigian ◽  
Johanna Bendell ◽  
Emiliano Calvo ◽  
Joseph W. Kim ◽  
Paolo A. Ascierto ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Objective Response ◽  
Locally Advanced ◽  
Survival Rates ◽  
Progression Free Survival ◽  
The United States ◽  
Phase Iii ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Esophagogastric Cancer

Purpose Metastatic esophagogastric cancer treatments after failure of second-line chemotherapy are limited. Nivolumab demonstrated superior overall survival (OS) versus placebo in Asian patients with advanced gastric or gastroesophageal junction cancers. We assessed the safety and efficacy of nivolumab and nivolumab plus ipilimumab in Western patients with chemotherapy-refractory esophagogastric cancers. Patients and Methods Patients with locally advanced or metastatic chemotherapy–refractory gastric, esophageal, or gastroesophageal junction cancer from centers in the United States and Europe received nivolumab or nivolumab plus ipilimumab. The primary end point was objective response rate. The association of tumor programmed death-ligand 1 status with response and survival was also evaluated. Results Of 160 treated patients (59 with nivolumab 3 mg/kg, 49 with nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, 52 with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg), 79% had received two or more prior therapies. At the data cutoff, investigator-assessed objective response rates were 12% (95% CI, 5% to 23%), 24% (95% CI, 13% to 39%), and 8% (95% CI, 2% to 19%) in the three groups, respectively. Responses were observed regardless of tumor programmed death-ligand 1 status. With a median follow-up of 28, 24, and 22 months across the three groups, 12-month progression-free survival rates were 8%, 17%, and 10%, respectively; 12-month OS rates were 39%, 35%, and 24%, respectively. Treatment-related grade 3/4 adverse events were reported in 17%, 47%, and 27% of patients in the three groups, respectively. Conclusion Nivolumab and nivolumab plus ipilimumab demonstrated clinically meaningful antitumor activity, durable responses, encouraging long-term OS, and a manageable safety profile in patients with chemotherapy-refractory esophagogastric cancer. Phase III studies evaluating nivolumab or nivolumab plus ipilimumab in earlier lines of therapy for esophagogastric cancers are underway.

scholarly journals Induction Chemotherapy Followed by Cetuximab Radiotherapy Is Not Superior to Concurrent Chemoradiotherapy for Head and Neck Carcinomas: Results of the GORTEC 2007-02 Phase III Randomized Trial

2018 ◽  
Vol 36 (31) ◽  
pp. 3077-3083 ◽  
Author(s):  
Lionnel Geoffrois ◽  
Laurent Martin ◽  
Dominique De Raucourt ◽  
Xu Shan Sun ◽  
Yungan Tao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Free Survival

Purpose Both concurrent chemoradiotherapy (CT-RT) and cetuximab radiotherapy (cetux-RT) have been established as the standard of care for the treatment of locally advanced squamous cell carcinoma of the head and neck. It was not known whether the addition of induction chemotherapy before cetux-RT could improve outcomes compared with standard of care CT-RT. Patients and Methods The current trial was restricted to patients with nonmetastatic N2b, N2c, or N3 squamous cell carcinoma of the head and neck and fit for taxotere, cisplatin, fluorouracil (TPF). Patients were randomly assigned to receive three cycles of TPF followed by cetux-RT versus concurrent carboplatin fluorouracil and RT as recommended in National Comprehensive Cancer Network guidelines. The trial was powered to detect a hazard ratio (HR) of 0.66 in favor of TPF plus cetux-RT for progression-free survival at 2 years. The inclusion of 180 patients per arm was needed to achieve 80% power at a two-sided significance level of .05. Results Between 2009 and 2013, 370 patients were included. All patients and tumors characteristics were well balanced between arms. There were more cases of grade 3 and 4 neutropenia in the induction arm, and the induction TPF was associated with 6.6% treatment-related deaths. With a median follow-up of 2.8 years, 2-year progression-free survival was not different between both arms (CT-RT, 0.38 v TPF + cetux-RT, 0.36; HR, 0.93 [95% CI, 0.73 to 1.20]; P = .58). HR was 0.98 (95% CI, 0.74 to 1.3; P = .90) for locoregional control and 1.12 (95% CI, 0.86 to 1.46; P = .39) for overall survival. These effects were observed regardless of p16 status. The rate of distant metastases was lower in the TPF arm (HR, 0.54 [95% CI, 0.30 to 0.99]; P = .05). Conclusion Induction TPF followed by cetux-RT did not improve outcomes compared with CT-RT in a population of patients with advanced cervical lymphadenopathy.

Once-a-Week Versus Once-Every-3-Weeks Cisplatin Chemoradiation for Locally Advanced Head and Neck Cancer: A Phase III Randomized Noninferiority Trial

2018 ◽  
Vol 36 (11) ◽  
pp. 1064-1072 ◽  
Author(s):  
Vanita Noronha ◽  
Amit Joshi ◽  
Vijay Maruti Patil ◽  
Jaiprakash Agarwal ◽  
Sarbani Ghosh-Laskar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Head And Neck ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Absolute Difference ◽  
Comparable Efficacy ◽  
Advanced Head ◽  
Adjuvant Setting ◽  
Free Survival

Purpose Chemoradiation with cisplatin 100 mg/m2 given once every 3 weeks is the standard of care in locally advanced head and neck squamous cell cancer (LAHNSCC). Increasingly, low-dose once-a-week cisplatin is substituted because of perceived lower toxicity and convenience. However, there is no level 1 evidence of comparable efficacy to cisplatin once every 3 weeks. Patients and Methods In this phase III randomized trial, we assessed the noninferiority of cisplatin 30 mg/m2 given once a week compared with cisplatin 100 mg/m2 given once every 3 weeks, both administered concurrently with curative intent radiotherapy in patients with LAHNSCC. The primary end point was locoregional control (LRC); secondary end points included toxicity, compliance, response, progression-free survival, and overall survival. Results Between 2013 and 2017, we randomly assigned 300 patients, 150 to each arm. Two hundred seventy-nine patients (93%) received chemoradiotherapy in the adjuvant setting. At a median follow-up of 22 months, the estimated cumulative 2-year LRC rate was 58.5% in the once-a-week arm and 73.1% in the once-every-3-weeks arm, leading to an absolute difference of 14.6% (95% CI, 5.7% to 23.5%); P = .014; hazard ratio (HR), 1.76 (95% CI, 1.11 to 2.79). Acute toxicities of grade 3 or higher occurred in 71.6% of patients in the once-a-week arm and in 84.6% of patients in the once-every-3-weeks arm ( P = .006). Estimated median progression-free survival in the once-a-week arm was 17.7 months (95% CI, 0.42 to 35.05 months) and in the once-every-3-weeks arm, 28.6 months (95% CI, 15.90 to 41.30 months); HR, 1.24 (95% CI, 0.89 to 1.73); P = .21. Estimated median overall survival in the once-a-week arm was 39.5 months and was not reached in the once-every-3-weeks arm (HR, 1.14 [95% CI, 0.79 to 1.65]; P = .48). Conclusion Once-every-3-weeks cisplatin at 100 mg/m2 resulted in superior LRC, albeit with more toxicity, than did once-a-week cisplatin at 30 mg/m2, and should remain the preferred chemoradiotherapy regimen for LAHNSCC in the adjuvant setting.

scholarly journals Phase III Randomized Trial of Induction Chemotherapy in Patients With N2 or N3 Locally Advanced Head and Neck Cancer

2014 ◽  
Vol 32 (25) ◽  
pp. 2735-2743 ◽  
Author(s):  
Ezra E.W. Cohen ◽  
Theodore G. Karrison ◽  
Masha Kocherginsky ◽  
Jeffrey Mueller ◽  
Robyn Egan ◽  
...  
Keyword(s):  
Head And Neck ◽  
Induction Chemotherapy ◽  
Locally Advanced ◽  
Phase Iii ◽  
Serious Adverse Events ◽  
Free Survival ◽  
Distant Failure ◽  
Common Grade ◽  
Treatment Naïve ◽  
Grade 3

Purpose Induction chemotherapy (IC) before radiotherapy lowers distant failure (DF) rates in locally advanced squamous cell carcinoma of the head and neck (SCCHN). The goal of this phase III trial was to determine whether IC before chemoradiotherapy (CRT) further improves survival compared with CRT alone in patients with N2 or N3 disease. Patients and Methods Treatment-naive patients with nonmetastatic N2 or N3 SCCHN were randomly assigned to CRT alone (CRT arm; docetaxel, fluorouracil, and hydroxyurea plus radiotherapy 0.15 Gy twice per day every other week) versus two 21-day cycles of IC (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2 on days 1 to 5) followed by the same CRT regimen (IC + CRT arm). The primary end point was overall survival (OS). Secondary end points included DF-free survival, failure pattern, and recurrence-free survival (RFS). Results A total of 285 patients were randomly assigned. The most common grade 3 to 4 toxicities during IC were febrile neutropenia (11%) and mucositis (9%); during CRT (both arms combined), they were mucositis (49%), dermatitis (21%), and leukopenia (18%). Serious adverse events were more common in the IC arm (47% v 28%; P = .002). With a minimum follow-up of 30 months, there were no statistically significant differences in OS (hazard ratio, 0.91; 95% CI, 0.59 to 1.41), RFS, or DF-free survival. Conclusion IC did not translate into improved OS compared with CRT alone. However, the study was underpowered because it did not meet the planned accrual target, and OS was higher than predicted in both arms. IC cannot be recommended routinely in patients with N2 or N3 locally advanced SCCHN.

A phase III multi-institutional randomized study of immunization with the gp100: 209–217(210M) peptide followed by high-dose IL-2 compared with high-dose IL-2 alone in patients with metastatic melanoma

2009 ◽  
Vol 27 (18_suppl) ◽  
pp. CRA9011-CRA9011 ◽  
Author(s):  
D. J. Schwartzentruber ◽  
D. Lawson ◽  
J. Richards ◽  
R. M. Conry ◽  
D. Miller ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Nature Medicine ◽  
Randomized Study ◽  
Locally Advanced ◽  
Peptide Vaccine ◽  
Progression Free Survival ◽  
Hla Typing ◽  
Phase Iii ◽  
High Dose ◽  
Free Survival

CRA9011 Background: In a phase II study, 13 (42%) of 31 patients with metastatic melanoma receiving high-dose (HD) IL-2 plus gp100:209–217(210M) peptide experienced objective responses (S.A. Rosenberg, et al, Nature Medicine 4: 321–327, 1998). Other studies showed a lower response rate (RR) but no randomized studies have been done. Methods: A prospective randomized phase III trial was conducted at 21 centers with 185 patients. Eligibility: stage IV or locally advanced stage III cutaneous melanoma, HLA A0201, no brain metastases, eligible for HD IL-2, and no previous HD IL-2 or gp100:209–217(210M). Arm 1 received HD IL-2 alone (720,000 IU/kg/dose) and Arm 2 gp100:209–217(210M) peptide + Montanide ISA followed by HD IL-2. The primary objective was clinical response. Secondary objectives were toxicity, disease free/progression free survival, immunologic response and quality of life. Central HLA typing, pathology review, and blinded response assessment were done at the NIH. Central data monitoring was done by The EMMES Corp. and a Data Safety Monitoring Board. Results: Numbers of patients enrolled, treated, and evaluable for response in Arm 1 were 94, 93, and 93 respectively; in Arm 2 91, 86, and 86. Toxicities were consistent with HD IL-2 ± vaccine. Investigator assessed RR showed significant improvement in overall RR for Arm 2=22.1% vs 9.7% (P=0.0223, Chi-Square) and progression free survival (PFS) in favor of Arm 2=2.9 months (1.7–4.5) vs 1.6 (1.5–1.8) (P=0.0101). Median overall survival favors Arm 2=17.6 months (11.8–26.6) vs 12.8 (8.7–16.3) (P=0.0964). Blinded response review is ongoing. Conclusions: RR and PFS were superior with peptide vaccine and HD IL-2 compared to HD IL-2 alone. This represents the first evidence of clinical benefit of vaccination in patients with melanoma. [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]

Neutrophil count and efficacy of chemoradiation in patients with locally advanced unresectable pancreatic carcinoma: An ancillary study of in the LAP 07 trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4120-4120 ◽  
Author(s):  
Antoine Schernberg ◽  
Dewi Vernerey ◽  
David Goldstein ◽  
Jean Luc Van Laethem ◽  
Bengt Glimelius ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Systemic Inflammation ◽  
Local Control ◽  
Neutrophil Count ◽  
External Validation ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Phase Iii

4120 Background: Predictive biomarkers of Overall Survival (OS) and Progression Free Survival (PFS) in locally advanced pancreatic cancer (LAPC) pts are mandatory. Baseline leukocyte, neutrophil and monocyte counts in addition to lymphocyte ratio (NLR) may predict OS in LAPC pts. Efficacy of chemoradiation (CRT) depending on neutrophil count was retrospectively analyzed in the largest Phase III cohort of LAPC. Methods: The international multicenter randomized LAP07 phase III trial (NCT00634725) has recruited 442 LAPC pts. We have studied the predictive and prognostic value of systemic inflammation, as defined: (i) baseline neutrophilia (neutrophil count > 7 G/L at first randomization) or (ii)increased absolute neutrophil count (IANC) after induction chemotherapy vs baseline. Univariate and multivariate Cox analysis evaluated the benefit of CRT for OS, PFS and Local Control (LC) in pts without systemic inflammation. Results: Patients with baseline neutrophilia (11%) had a worse OS (median 8.9 vs 13.3 months, p = 0.01). At 2nd randomization, 9% and 29% pts had baseline neutrophilia or IANC, respectively. Both neutrophilia (median OS 10.6 vs 16.1 months, p = 0.03) and IANC (median OS 14.6 vs 17.4 months, p = 0.02) predicted poor OS. Systemic inflammation predicted local resistance to CRT (p = 0.02, interaction = 0.015). After excluding pts with systemic inflammation, 1-year local control was 80% in CRT vs 54% in chemotherapy arms (p < 0.001). Pts without systemic inflammation in CRT arm had improved PFS vs chemotherapy arm (median 10.3 vs 8.3 months, p = 0.04). In multivariate analysis in this population, CRT increased PFS (HR = 0.66, 95%CI: 0.45 - 0.97, p = 0.03), after adjusting on age, tumor size, pain at enrollment, albumin, and CA 19.9 according to PROLAP nomogram parameters. Conclusions: In LAPC pts with tumor controlled after induction chemotherapy, systemic inflammation may help to better predict those who will benefit from CRT. This result may impact clinical management and the design of future clinical trials for LAPC. An external validation with a cohort from the ARCAD pancreas meta-analysis is under consideration. Clinical trial information: NCT00634725.

Safety and efficacy of docetaxel combined with cisplatin as induction chemotherapy followed by cisplatin concurrent chemoradiotherapy plus gemcitabine as adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: A prospective and multicenter phase II trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6064-6064
Author(s):  
Zhi Hui Wang ◽  
Peijian Peng ◽  
Siyang Wang ◽  
Yumeng Liu ◽  
Zhong Lin
Keyword(s):  
Radiation Therapy ◽  
Adjuvant Chemotherapy ◽  
Induction Chemotherapy ◽  
Treatment Strategy ◽  
Objective Response ◽  
Locally Advanced ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Free Survival ◽  
Safety And Efficacy

6064 Background: Radiation therapy is the only curative treatment modality for nonmetastatic nasopharyngeal cancer (NPC). Concurrent chemoradiation (CCRT) is the standard treatment strategy for NPC in locally advanced stages. However, the results after such treatment are suboptimal. Clearly, novel treatment strategies are needed to further improve patients’ survival rates. This trial aimed to determine the safety and efficacy of a new treatment strategy. Methods: Patients with stage III – IVa-b NPC received TP (docetaxel 75 mg/m2, cisplatin 75 mg/m2 every 3 weeks for 2-3 cycles) followed by cisplatin chemotherapy concurrently with either 3-dimentional conformal radiation therapy or intensity-modulated radiation therapy plus gemcitabine (1000mg/m2 every 2 weeks for 2 cycles) as adjuvant chemotherapy. Objective response rates and acute toxicity were assessed based on RECIST (1.1) and CTCAE v.4.0, respectively. Kaplan-Meier analysis was used to calculate survival rates. This trial is registered with the Chinese Clinical Trials Registry, number ChiCTR-OIC-17011464. Results: From July 2010 to July 2017, 20 eligible patients with nonmetastatic stage III-IVb NPC were enrolled. The objective response rates were 90% (3 complete responses [CRs] and 15 partial responses [PRs]) after two or three cycles of induction chemotherapy (ICT) and 100% (17 CRs and three PRs) after CCRT plus gemcitabine adjuvant chemotherapy, respectively. With a median follow-up time of 41 months, the 3-year overall survival rates were 90% (18/20,95% confidence interval [CI], 76.9%-100%).The 3-year progression-free survival, distant metastasis-free survival, and local progression-free survival rates were 80% (16/20,95% CI, 62.5%-97.5%), 85% (17/20,95% CI, 69.4%-100%),95% (19/20,95% CI, 85,4%-100%), respectively. The most frequent grade 3–4 toxicities were neutropenia (3/20,15%) and nausea (2/20,10%) after ICT and thrombocytopenia (6/20,30%) and leukopenia (6/20,30%) after CCRT plus gemcitabine adjuvant chemotherapy. Conclusions: Neoadjuvant TP followed by concurrent chemoradiation plus gemcitabine as adjuvant chemotherapy was well tolerated and produced promising outcomes in patients with LA-NPC in this hypothesis-generating study. The authors concluded that randomized controlled trials are warranted to definitively confirm this aggressive and potentially efficacious strategy. Clinical trial information: ChiCTR-OIC-17011464.

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]

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