Perioperative FLOT is a standard of care for resectable, esophagogastric adenocarcinoma (EGA). This trial evaluates the addition of trastuzumab (tras) and pertuzumab (per) to FLOT for HER2-positive patients (pts).
PETRARCA is a multicenter, randomized, investigator initiated trial planned as a phase II/III study. We report the phase II part of this trial. Pts with HER2+ resectable EGA (≥ cT2 or cN+) were randomized 1:1 to 4 pre- and post-operative cycles of FLOT (Docetaxel 50 mg/m2; Oxaliplatin 85 mg/m2; Leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2w) (Arm A) or the same regimen with tras 8/6 mg/kg and per 840 mg q3w, followed by 9 cycles tras/per (arm B). Primary endpoint for the phase II part was the rate of pathological complete remission (pCR). Main secondary endpoints were DFS, OS and safety.
The trial closed prematurely and did not proceed to phase III. In total, 81 pts were randomized (A, 41; B, 40). Baseline characteristics were balanced (overall, male 79%; median age 60; cT3/T4 86%; cN+ 85%; GEJ 75%). 93% in arm A and 90% in arm B completed pre-OP treatment as planned. More pts had at least one dose modification in arm B (A, 44%; B, 70%). pCR rate was significantly improved with tras/per (A, 12%; B, 35%; p = 0.02). Likewise, the rate of pathological lymph node negativity was higher with tras/per (A, 39%; B, 68%). R0-resection rate (A, 90%; B, 93%) and surgical morbidity (A: 43%; B, 44%) were comparable. Moreover, in-house mortality was equal in both arms (overall 2.5%). Median DFS was 26 months in arm A and not yet reached in arm B (HR 0.58, p = 0.14). After a median follow-up of 22 months median OS was not yet reached. DFS and OS rates [with 95% CI] at 24 months were 54% [38-71%] and 77% [63-90%] in arm A and 70% [55-85%] and 84% [72-96%] in arm B, respectively. More ≥ grade 3 adverse events were reported with tras/per (75% vs. 85%), especially diarrhea (5% vs. 41%) and leukopenia (13% vs 23%).
The addition of tras/per to perioperative FLOT significantly improved pCR and nodal negativity rates in pts with Her2+ resectable EGA at the price of higher rates of diarrhea and leukopenia. Subgroup analyses will be presented.
NCT02581462; EudraCT: 2014-002695-86.
Institut für Klinische Krebsforschung IKF GmbH.
Roche.
S-E. Al-Batran: Advisory/Consultancy: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Lilly; Advisory/Consultancy: Bristol-Myers Squibb ; Advisory/Consultancy, Research grant/Funding (self): Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony: Nordic Bioscience; Advisory/Consultancy: Merck Sharp & Dohme ; Speaker Bureau/Expert testimony: AIO gGmbH ; Speaker Bureau/Expert testimony: Forum für Medizinische Fortbildung ; Speaker Bureau/Expert testimony: MCI group ; Research grant/Funding (self): Medac; Research grant/Funding (self): Hospira; Research grant/Funding (self): Sanofi; Research grant/Funding (self): German Cancer Aid ; Research grant/Funding (self): German Research Foundation ; Research grant/Funding (self): Federal Ministry of Education and Research ; Research grant/Funding (self): Roche; Research grant/Funding (self): Vifor. G.M. Haag: Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy: Esocap; Honoraria (self): Servier; Research grant/Funding (institution): Nordic Pharma; Research grant/Funding (institution): Taiho Pharmaceutical; Travel/Accommodation/Expenses: Lilly. T.J. Ettrich: Advisory/Consultancy: Merck Serono ; Advisory/Consultancy: Sanofi; Advisory/Consultancy: BMS; Advisory/Consultancy: Bayer; Advisory/Consultancy: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy: Eisai; Advisory/Consultancy: MSD; Travel/Accommodation/Expenses: Ipsen; Research grant/Funding (self): Baxalta/Shire . K. Borchert: Advisory/Consultancy, Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy: Merck; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Servier; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen. A. Kretzschmar: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche. G.M. Siegler: Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Celgene; Travel/Accommodation/Expenses: Eisai; Travel/Accommodation/Expenses: Sanofi; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Lilly. E. Goekkurt: Advisory/Consultancy: MSD; Advisory/Consultancy: Servier; Advisory/Consultancy: BMS; Advisory/Consultancy: Roche; Advisory/Consultancy: Sanofi. R.J.C. Mahlberg: Honoraria (self): Roche; Honoraria (self), Travel/Accommodation/Expenses: Amgen; Honoraria (self): Novartis; Travel/Accommodation/Expenses: Merck; Travel/Accommodation/Expenses: Pfizer. D. Pink: Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Clinigen Group; Advisory/Consultancy, Research grant/Funding (institution): Roche; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): PharmaMar. W.O. Bechstein: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Integra LifeSciences ; Honoraria (self), Travel/Accommodation/Expenses: Baxter; Honoraria (self), Travel/Accommodation/Expenses: Chiesi; Honoraria (self), Travel/Accommodation/Expenses: MCI Deutschland ; Honoraria (self), Travel/Accommodation/Expenses: Medupdate; Honoraria (self), Travel/Accommodation/Expenses: Merck Serono ; Honoraria (self), Travel/Accommodation/Expenses: Teva. P. Reichardt: Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Clinigen Group ; Honoraria (self), Advisory/Consultancy: Lilly; Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Bayer; Advisory/Consultancy: Deciphera ; Honoraria (self): Amgen. T.O. Goetze: Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy: MSD Oncology ; Advisory/Consultancy: Bayer; Advisory/Consultancy: Servier; Advisory/Consultancy: Roche; Research grant/Funding (self): Deutsche Forschungsgemeinschaft ; Research grant/Funding (self): Gemeinsamer Bundesausschuss . R.D. Hofheinz: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche. All other authors have declared no conflicts of interest.
T-DXd is an antibody-drug conjugate consisting of an anti-HER2 antibody, a cleavable tetrapeptide-based linker, and a membrane-permeable topoisomerase I inhibitor payload. T-DXd is approved for the treatment of HER2-positive metastatic breast cancer in the US and Japan. T-DXd increased confirmed ORR (42.9% vs 12.5%) and OS (median, 12.5 vs 8.4 mo; HR, 0.59;
Pts with centrally confirmed HER2-low (IHC 2+/ISH− [cohort 1] or IHC 1+ [cohort 2] on archival tissue) that progressed on ≥ 2 prior lines of therapy were enrolled in Japan and Korea. Pts were excluded if they had prior HER2 therapy. The primary endpoint was ORR by independent central review.
20 (cohort 1) and 24 (cohort 2) pts were treated with T-DXd 6.4 mg/kg q3w. Most were from Japan (cohort 1, 80.0%; cohort 2, 79.2%) and had received a median of 2 prior lines of therapy. At data cutoff (8 Nov 2019), no pts in cohort 1 and 2 in cohort 2 (8.3%) remained on treatment (median duration, 4.2 and 2.8 mo). In cohort 1, confirmed ORR was 26.3% (5/19, all PR); 12 pts had stable disease (DCR, 89.5%). Median PFS was 4.4 mo (95% CI, 2.7-7.1 mo); median OS was 7.8 mo (95% CI, 4.7 mo-NE), with a 12-mo OS rate of 40.0%. Confirmed ORR in cohort 2 was 9.5% (2/21, all PR); confirmed DCR was 71.4%. Median PFS and OS were 2.8 mo (95% CI, 1.5-4.3 mo) and 8.5 mo (95% CI, 4.3-10.9 mo), with a 12-mo OS rate of 25.7%. Grade ≥ 3 adverse events occurred in 70.0% and 79.2% of pts in cohorts 1 and 2. Decreased appetite (65.0%; 75.0%), nausea (55.0%; 79.2%), and neutrophil count decreased (45.0%; 50.0%) were most common. One pt in each cohort (grade 1 = 1; grade 2 = 1) had T-DXd–related interstitial lung disease.
T-DXd showed preliminary evidence of clinical activity in pts with previously treated, HER2-low gastric or GEJ cancer. The safety profile was similar to that in the HER2+ primary cohort.
NCT03329690.
Medical editorial assistance provided by John Togneri, PhD (Articulate Science LLC).
Daiichi Sankyo Co., Ltd.
Daiichi Sankyo Co., Ltd.
K. Yamaguchi: Speaker Bureau/Expert testimony, Research grant/Funding (institution): Cancer Institute Hospital of Japanese Foundation for Cancer Research; Honoraria (institution), Speaker Bureau/Expert testimony: Daiichi Sankyo ; Honoraria (institution), Speaker Bureau/Expert testimony: Taiho Pharmaceutical; Honoraria (institution), Speaker Bureau/Expert testimony: Chugai Pharm; Speaker Bureau/Expert testimony: Bristol-Myers Squibb Japan; Honoraria (institution), Speaker Bureau/Expert testimony: Ono Pharmaceutical; Speaker Bureau/Expert testimony: Takeda; Honoraria (institution), Speaker Bureau/Expert testimony: Lilly; Honoraria (institution), Speaker Bureau/Expert testimony: Sanofi; Honoraria (institution): MSD oncology; Honoraria (institution): Dainippon Sumitomo Pharma; Honoraria (institution): Gilead Sciences; Honoraria (institution): Boehringer Ingelheim; Honoraria (institution): Eisai; Honoraria (institution): Yakult Honsha. Y-J. Bang: Advisory/Consultancy: Samyung; Advisory/Consultancy, Research grant/Funding (institution): BeiGene; Advisory/Consultancy, Research grant/Funding (institution): Green Cross; Advisory/Consultancy, Research grant/Funding (institution): Taiho Pharmaceutical; Advisory/Consultancy, Research grant/Funding (institution): Merck Serono; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca/MedImmune; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): MSD Oncology; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Hanmi; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (institution): Astellas Pharma; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Genexine; Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Boston Biomedical; Research grant/Funding (institution): Five Prime Therapeutics; Research grant/Funding (institution): Chong Kun Dang Pharmaceutical; Research grant/Funding (institution): Ono Pharmaceutical; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Curis. S. Iwasa: Research grant/Funding (institution): Daiichi Sankyo . N. Sugimoto: Research grant/Funding (institution): Daiichi Sankyo ; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Solasia; Research grant/Funding (institution): ONO; Research grant/Funding (self): Lilly; Research grant/Funding (self): Taiho. M-H. Ryu: Honoraria (self), Advisory/Consultancy: ONO; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Lilly ; Honoraria (self), Advisory/Consultancy: Taiho; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Daehwa Pharmaceutical . D. Sakai: Speaker Bureau/Expert testimony, Research grant/Funding (institution): Chugai Pharma; Research grant/Funding (institution): Yakult Honsha; Research grant/Funding (institution): Ono Pharmaceutical; Research grant/Funding (self): Daiichi Sankyo; Research grant/Funding (self): Lilly Japan. H.C. Chung: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck-Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Taiho; Advisory/Consultancy: Celltrion; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy: Quintiles; Advisory/Consultancy, Research grant/Funding (institution): BMS/Ono; Advisory/Consultancy, Research grant/Funding (institution): Beigene; Advisory/Consultancy: Gloria; Advisory/Consultancy: AMGEN; Research grant/Funding (institution): GSK. H. Kawakami: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Bristol and Myers Squibb; Honoraria (self), Advisory/Consultancy: Ono pharmaceutical ; Honoraria (self), Advisory/Consultancy: Eli Lilly Japan; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Taiho; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self): Takeda; Research grant/Funding (institution): Eisai; Honoraria (self), Advisory/Consultancy: MSD KK. J. Lee: Advisory/Consultancy: Oncologie; Advisory/Consultancy: Seattle Genetics; Research grant/Funding (self): Astra Zeneca; Research grant/Funding (self): Merck Sharp and Dohme; Research grant/Funding (self): Eli Lilly and Company. K. Saito, T. Kamio, M. Sugihara: Full/Part-time employment: Daiichi Sankyo. Y. Kawaguchi: Shareholder/Stockholder/Stock options, Full/Part-time employment: Daiichi Sankyo . A. Kojima: Shareholder/Stockholder/Stock options, Full/Part-time employment: Daiichi Sankyo . K. Shitara: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Abbvie; Honoraria (self): Yakult; Advisory/Consultancy, Research grant/Funding (institution): Astellas Pharma; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Takeda; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical; Advisory/Consultancy, Research grant/Funding (institution): Taiho Pharmaceutica; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline; Advisory/Consultancy, Research grant/Funding (institution): Chugai Pharm; Research grant/Funding (institution): Medi Science; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Dainippon Sumitomo Pharma. All other authors have declared no conflicts of interest.
In JACOB (NCT01774786), a double-blind, placebo-controlled, randomised, multicentre, phase III study in patients (pts) with HER2-positive mGC/GEJC, addition of P to H + CT did not significantly improve overall survival (OS)
Pts with previously untreated disease were randomised 1:1 to P + H + CT or PLA + H + CT. P (840 mg) + H (8 mg/kg loading and 6 mg/kg maintenance doses) were given intravenously every 3 weeks until disease progression or unacceptable toxicity. CT was a standard cisplatin/fluoropyrimidine regimen. The primary endpoint was OS. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR) and safety. All results are considered descriptive.
The date of this database lock snapshot was 24 Jan 2020. Overall, 388 pts were randomised to P + H + CT The incidence of symptomatic left ventricular systolic dysfunction / heart failure was low and similar in both arms (P + H + CT: 0.8%; PLA + H + CT: 0.3%). The incidence of all-grade diarrhoea was higher in the P + H + CT arm (62.6%
PLA + H + CT (n = 392) P + H + CT (n = 388) Efficacy Median OS, m 14.2 18.1 Stratified HR (95% CI) 0.85 (0.72, 0.99) Median duration of follow-up, m 44.4 46.1 Median PFS, m 7.2 8.5 Stratified HR (95% CI) 0.73 (0.62, 0.85) Median duration of follow-up, m 47.4 50.4 Baseline measurable disease n = 352 n = 351 ORR, % (CR + PR) 48.6 57.0 Median DoR, m (95% CI) n = 175 8.4 (6.8, 9.1) n = 203 10.2 (8.5, 12.0) Safety, pts (%) n = 388 N = 385 AE 385 (99.2) 381 (99.0) AE with fatal outcome 31 (8.0) 27 (7.0) Serious AE 156 (40.2) 178 (46.2) Grade ≥ 3 AE 288 (74.2) 310 (80.5) AE leading to P/PLA + H discontinuation 46 (11.9) 48 (12.5) AE leading to P/PLA dose interruption and / or delay 94 (24.2) 110 (28.6)
The end-of-study analysis from JACOB confirmed evidence of treatment activity, with a 15% reduction in risk of death when adding P to H + CT in previously untreated pts with mGC/GEJC. The overall safety profile of P + H + CT was considered acceptable.
NCT01774786.
Support for third-party writing assistance for this abstract, furnished by Islay Steele, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.
F. Hoffmann-La Roche Ltd.
F. Hoffmann-La Roche Ltd.
J. Tabernero: Advisory/Consultancy: Scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono; Advisory/Consultancy: Scientific consultancy role for Merrimack, Merus, Molecular Partners, Novartis, Peptomyc, Pfizer, Pharmacyclics, ProteoDesign SL, Rafael Pharmaceuticals, F. Hoffmann-La Roche Ltd, Sanofi, SeaGen, Seattle Genetics, Servier, Symphogen, Taiho, VCN Bioscience; Advisory/Consultancy: Scientific consultancy role for Biocartis, Foundation Medicine, HalioDX SAS and Roche Diagnostics; Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland. P.M. Hoff: Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland; Research grant/Funding (self): F. Hoffmann-La Roche Ltd. L. Shen: Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland; Research grant/Funding (self): F. Hoffmann-La Roche Ltd; Advisory/Consultancy: F. Hoffmann-La Roche Ltd. A. Ohtsu: Research grant/Funding (self): BMS; Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland; Non-remunerated activity/ies: Personal fees from BMS, Ono, Taiho and Chugai. M.A. Shah: Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland; Research grant/Funding (self): Astellas, Merck, Boston Biomedical. A. Siddiqui: Full/Part-time employment: Roche Products Limited; Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland. S. Heeson: Shareholder/Stockholder/Stock options: F. Hoffman-La Roche Ltd; Full/Part-time employment: Roche Products Limited; Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland. H. Wu: Shareholder/Stockholder/Stock options: F. Hoffman-La Roche Ltd; Full/Part-time employment: Roche (China) Holding Ltd; Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland. E. Restuccia: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche, Basel, Switzerland; Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland. Y-K. Kang: Advisory/Consultancy: Taiho, Ono, Merck, Daehwa, BMS, Astellas, Zymeworks, Alx Oncology, Amgen, Novartis, Macrogenics, Surface Oncology; Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland.
Periop. FLOT has become SOC for resectable, esophagogastric adenocarcinoma (EGA). However, patient’s outcome is still poor. This trial evaluates the addition of the VEGF-R2 inhibitor ramucirumab (RAM) to FLOT.
This is a prospective, international, randomized, investigator-initiated phase II/III trial. Patients (pts) with resectable, Her2-negative EGA(≥ cT2 or cN+) were randomized to 4 pre-and post-operative cycles of FLOT (docetaxel 50 mg/m2; oxaliplatin 85 mg/m2; leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2w) alone (Arm A) or FLOT with RAM 8mg/kg q2w, followed by 16 cycles RAM (Arm B, FLOT-RAM). Here, we report the main results along with the subgroup analysis explaining the higher rate of R0-resection in the FLOT-RAM arm.
In total, 180 pts (FLOT, 91; FLOT-RAM, 89) were randomized. Baseline characteristics were similar between arms (male, 73%; median age, 60y; cT3/T4, 83%; cN+, 78%; GEJ, 54%). The rate of signet-ring cell cancer was high (40%). As reported at ASCO, no difference in path response rates was seen (FLOT, 30%; FLOT-RAM, 27%). However, FLOT-RAM significantly improved R0-resection rate (FLOT, 82%; FLOT-RAM, 96%, p=0.0078). This difference was due to less pts in the FLOT-RAM arm with disease progression prior to operation (FLOT, 6%; FLOT-RAM, 1%), more pts proceeding to operation (FLOT, 93%; FLOT-RAM, 97%), more pts receiving resectional surgery (FLOT, 88%; FLOT-RAM, 97%), and less pts having residual tumor out of the resected pts (FLOT, 4; FLOT-RAM, 1). In the subgroup analysis, the relative benefit of FLOT-RAM in terms of R0-resection was seen in all groups but was a bit pronounced in the cT3/T4 group (FLOT, 80%; FLOT-RAM, 97%), specifically the T4 (FLOT, 1/4 [25%]; FLOT-RAM, 8/8 [100%]) and the diffuse/mixed type histology (FLOT, 77%; FLOT-RAM, 95%).
FLOT-RAM significantly improved R0-resection rates in a patient group enriched with diffuse type and signet cell histology, mainly because more pts proceeded to operation, more pts received resectional surgery, and less pts had residual disease. The effects were pronounced in more advanced stage and the diffuse/mixed type histology.
NCT02661971; EudraCT: 2015-003118-26.
Institut für Klinische Krebsforschung IKF GmbH.
Lilly Deutschland GmbH.
S-E. Al-Batran: Advisory/Consultancy, Research grant/Funding (self): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Lilly; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (self): Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony: Nordic Bioscience; Advisory/Consultancy: Merck Sharp & Dohme; Speaker Bureau/Expert testimony: AIO gGmbH; Speaker Bureau/Expert testimony: Forum für Medizinische Fortbildung; Speaker Bureau/Expert testimony: MCI group; Shareholder/Stockholder/Stock options: IKF Klinische Krebsforschung; Research grant/Funding (self): Medac; Research grant/Funding (self): Hospira; Research grant/Funding (self): Sanofi; Research grant/Funding (self): German Cancer Aid ; Research grant/Funding (self): German Research Foundation; Research grant/Funding (self): Federal Ministry of Education and Research; Research grant/Funding (self): Vifor Pharma. R.D. Hofheinz: Honoraria (self), Advisory/Consultancy: Merck Serono ; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen ; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Sanofi ; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb ; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Honoraria (self), Speaker Bureau/Expert testimony: Lilly; Speaker Bureau/Expert testimony: Merck; Speaker Bureau/Expert testimony: SERVIER ; Honoraria (self), Research grant/Funding (institution): Medac ; Research grant/Funding (institution): German Cancer Aid. E. Goekkurt: Advisory/Consultancy: MSD; Advisory/Consultancy: Servier; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Roche; Advisory/Consultancy: Sanofi . D. Pink: Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Clinigen; Advisory/Consultancy, Research grant/Funding (institution): Roche; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): PharmaMar. G.M. Siegler: Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Eisai; Travel/Accommodation/Expenses: Celgene; Travel/Accommodation/Expenses: Sanofi; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Lilly. E. Maiello: Advisory/Consultancy: Astra Zeneca; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Servier; Advisory/Consultancy: Sanofi Genzyme; Advisory/Consultancy: Roche; Advisory/Consultancy: Merck; Advisory/Consultancy: Eisai; Advisory/Consultancy: Pfizer. T.O. Götze: Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy: MSD Oncology ; Advisory/Consultancy: Bayer; Advisory/Consultancy: SERVIER ; Advisory/Consultancy: Roche ; Research grant/Funding (self): Deutsche Forschungsgemeinschaft ; Research grant/Funding (self): Gemeinsamer Bundesausschuss . All other authors have declared no conflicts of interest.
Oral mucositis (OM) is an unpleasant adverse event in cancer patients receiving chemotherapy. A prospective multicenter feasibility study,
We conducted a phase III multicenter RCT to elucidate the preventive effect of ED against OM in patients with esophageal cancer (EC) receiving DCF (docetaxel, cisplatin, and 5-fluorouracil) therapy. Patients were randomly assigned to receive two cycles of DCF with (group A) or without (group B) ED (160 g/day) at a 1:1 ratio. The primary endpoint was the incidence of grade ≥ 2 OM assessed using
117 patients were enrolled and randomized; 4 failed to start treatment and were excluded from primary analysis; 55 and 58 patients were allocated to groups A and B, respectively. There was no significant difference in patients’ background. Grade ≥ 2 OM was demonstrated by 8 (14.5%) and 20 (34.5%) patients in groups A and B, respectively (
Our multi-institutional RCT shows that ED has a preventive effect on OM in patients with EC receiving chemotherapy.
jRCT s071180029.
The authors.
Japanese Foundation for Multidisciplinary Treatment of Cancer and EA Pharma Co., Ltd.
E. Otsuji: Research grant/Funding (institution), Endowed chair: Yakult Honsha Co., Ltd.. H. Baba: Research grant/Funding (institution): Yakult Honsha Co.,Ltd.. S. Morita: Honoraria (self): Bristol-Myers Squibb Company. Y. Kitagawa: Advisory/Consultancy: Ono Pharmaceutical Co., Ltd.; Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Taiho Pharmaceutical Co., Ltd; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Chugai Pharmaceutical Co., Ltd; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Yakult Honsha Co. Ltd.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Daiichi Sankyo Company, Limited; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Merck Serono Co., Ltd; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AsahiKASEI Co., Ltd.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): EA Pharma Co., Ltd; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Otsuka Pharmaceutical Co., Ltd; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Takeda Pharmaceutical Co., Ltd; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Otsuka Pharmaceutical Factory Inc.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Shionogi & Co., Ltd; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Kaken Pharmaceutical Co.,Ltd.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Astellas Pharma Inc.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Medicon Inc; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Dainippon Sumitomo Pharma Co., Ltd.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Taisho Toyama Pharmaceutical Co., Ltd.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Kyouwa Hakkou Kirin Co., Ltd.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Ono Pharmaceutical Co., Ltd.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Nihon Pharmaceutical Co., Ltd.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Japan Blood Products Organization; Speaker Bureau/Expert testimony, Research grant/Funding (self): Sanofi K.K.; Honoraria (self), Speaker Bureau/Expert testimony: Eisai Co., Ltd.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Tsumura & Co.; Research grant/Funding (self): Kowa Pharmaceutical Co., Ltd.; Research grant/Funding (self): Pfizer Japan Inc.; Research grant/Funding (self): Medtronic Japan Co., Ltd.; Research grant/Funding (self): Abbott Japan Co., Ltd; Research grant/Funding (self): Fujifilm Toyama Chemical Co., Ltd. K. Yoshida: Research grant/Funding (self): Sanofi K.K.; Research grant/Funding (self), no involvement in intellectual property: Yakult Honsha Co.,Ltd. All other authors have declared no conflicts of interest.