Cancers of the Esophagus and Stomach

Studies presented in oral sessions with links to abstracts and conclusions cited from abstracts:

 

First Author: Daishi Morimoto
Long-term outcome of a randomized phase III trial exploring the significance of extensive intraoperative peritoneal lavage in addition to standard treatment for ≥ T3 resectable gastric cancer: CCOG 1102.

Conclusions: Although EIPL for advanced gastric cancer was safe and suggested some efficacy, the primary endpoint designed based on the previous small-scale trial was not met. Clinical trial information: 000005907.

J Clin Oncol 36, 2018 (suppl 4S; abstr 1)


First Author: Basem Azab, BA
The impact of the chemoradiation to surgery interval on pathological complete response: Short and long-term overall survival in esophageal cancer patients.

Conclusions: Despite higher pCR rate as CRT-S interval increasing, surgery is preferred to be done in less than 65 days after CRT to avoid worse 90-day mortality and achieve better OS. Further randomized studies are needed to consolidate our findings.

J Clin Oncol 36, 2018 (suppl 4S; abstr 2)


First Author: Patrick Oh
Impact of lung and heart dose on survival after radiotherapy for esophageal cancer.

Conclusions: This comprehensive dosimetric analysis of heart and lung dose in a large cohort of esophageal cancer patients suggests that lung dose is a significant independent predictor of survival. Cardiac dose was not independently predictive after adjusting for lung dose and other clinical factors. This data suggests that esophageal cancer outcomes may be improved by minimizing lung dose, particularly the volume receiving 20Gy or more, and provides further rationale for pursuing new techniques to reduce lung dose, such as proton therapy.

J Clin Oncol 36, 2018 (suppl 4S; abstr 3)


First Author: Florian Lordick, MD
Intraperitoneal immunotherapy with the bispecific anti-EpCAM x anti-CD3 directed antibody catumaxomab for patients with peritoneal carcinomatosis from gastric cancer: Final results of a randomized phase II AIO trial.

Conclusions: 

i.p. CATU followed by i.v. FLOT was tolerable in patients with advanced GC and PC. Side effects with CATU were the following: nausea, fever, abdominal pain, and elevated liver enzymes (gGT & bilirubin). FLOT after CATU was equally tolerated as FLOT alone. A trend was observed towards a superior complete remission rate with CATU but no significance. Survival outcomes were not different between study arms and within expected range for stage IV GC.

Addition of i.p. CATU as part of a multimodal treatment approach revealed feasible and tolerable in patients with GC and PC. Although the primary endpoint was not met, the results are promising for future trials investigating i.p. immunotherapy in this patient population. Clinical trial information: NCT01504256

J Clin Oncol 36, 2018 (suppl 4S; abstr 4)


First Author: Charles Fuchs, MD
RAINFALL: A randomized, double-blind, placebo-controlled phase III study of cisplatin (Cis) plus capecitabine (Cape) or 5FU with or without ramucirumab (RAM) as first-line therapy in patients with metastatic gastric or gastroesophageal junction (G-GEJ) adenocarcinoma.

The results of the 645-patient RAINFALL trial showed only a 9-day improvement in PFS by adding this angiogenesis inhibitor to chemotherapy vs. chemotherapy alone (5.85 months vs. 5.55 months). There was no difference in overall survival (11.2 months vs.10.7 months), a secondary endpoint.

NCT02314117

J Clin Oncol 36, 2018 (suppl 4S; abstr 5)


First Author: Pieter Van Der Sluis
Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy versus open transthoracic esophagectomy for resectable esophageal cancer: A randomized controlled trial.

Conclusions: RAMIE resulted in a lower percentage of overall, surgery-related and (cardio)pulmonary complications with lower postoperative pain, better quality of life and a better short term postoperative functional recovery compared to OTE. Oncological outcomes were equal. This randomized controlled trial provides evidence for the use of RAMIE to improve postoperative outcome in patients with resectable esophageal cancer. Clinical trial information: NCT01544790

J Clin Oncol 36, 2018 (suppl 4S; abstr 6)


First Author: Nozomu Machida
A prospective multicenter trial of S-1 with lafutidine vs S-1 as adjuvant chemotherapy for gastric cancer in Japan: AEOLUS.

Conclusions: Lafutidine may increase a completion rate of adjuvant chemotherapy using S-1 within a 30% dose reduction for gastric cancer. This result need to be confirmed in double-blind placebo control study. Clinical trial information: UMIN000002703.

J Clin Oncol 36, 2018 (suppl 4S; abstrt 91)


First Author: Pierre Emmanuel Bonnot, MD
CYTO-CHIP: Cytoreductive surgery versus cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis: A propensity-score analysis from BIG RENAPE and FREGAT working groups.

Conclusions: Compared to CRSa, HIPEC was associated with increased OS and potential disease eradication for gastric cancer with PC, without additional morbidity. This treatment, when optimal CRS can be achieved, should be considered as the gold standard since outcomes remain grim with chemotherapies. Clinical trail information: NCT03253939

J Clin Oncol 36, 2018 (suppl 4S; abstr 8)


First Author: Maria Svensson
Associations of PD-1 and PD-L1 expression with mismatch repair status and prognosis in chemoradiotherapy-naïve esophageal and gastric adenocarcinoma.

Conclusions: High expression of PD-L1 but not PD-1 is significantly associated with MMR deficiency in EG cancer. High PD-L1 expression in TIC but not in TC, or high PD-1 expression in TIC, signifies a prolonged survival, in particular in MMR proficient tumours.

(J Clin Oncol 36, 2018 (suppl 4S; abstr 9)


 

Poster Presentation only:

M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGF-β, in Asian Patients With Pretreated Recurrent or Refractory Gastric Cancer: Preliminary Results From a Phase 1 Trial

 

M7824 (MSB0011359C) is an innovative first-in-class bifunctional fusion protein composed of a human IgG1 mAb against PD-L1 fused with 2 extracellular domains of TGF-β receptor II to function as a TGF-β “trap”. Preclinical studies in murine models indicate that M7824 improves antitumor activity compared with either an anti–PD-L1 antibody or TGF-β trap alone. Data from a phase 1, 3+3 dose-escalation study (NCT02517398) suggest that M7824 – administered at doses of 0.3, 1, 3, 10, or 20 mg/kg – has a manageable safety profile and shows encouraging early signs of clinical efficacy in patients with heavily pretreated advanced solid tumors.

Conclusions:

• Treatment with M7824 was associated with a manageable safety profile: a low rate of grade 3 TRAEs and no grade 4 events

– 1 grade 5 event (sudden death) was considered possibly related to treatment, but suspected rupture of pre-existing thoracic aortic aneurysm was cited as other probable cause by the investigator

• Early signs of clinical activity are encouraging in this study of Asian patients with heavily pretreated gastric cancer (all comer, PD-L1 unselected)

  • –  1 patient had confirmed CR (ongoing at 5.4+ months), 4 had PR (3 ongoing at data cutoff) with duration of response of 2.4, 3.6+, 5.4+, and 6.9+ months at cutoff, and 6 had SD

  • –  3 patients had unconfirmed PRs, 1 confirmed after data cutoff date and ongoing since October 4, 2017

  • –  Confirmed ORR is 19.4% (post database cutoff update); unconfirmed ORR is 25.8%

  • –  These preliminary results compare favorably to similar patient populations treated with PD-1/PD-L1 inhibitors, with ORRs that range from 11.2% in PD-L1 unselected12 to 13.3% in PD-L1 positive tumors

    • This phase 1 study is ongoing; additional biomarker analysis will be reported once available

J Clin Oncol 36, 2018 (suppl 4S; abstr 100)