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ASCO 2017 highlights and editor recommendations - Upper GI - Part 1

Selected ASCO 2017 abstracts in upper GI

  • KEYNOTE-059 cohort 2: Safety and efficacy of pembrolizumab (pembro) plus 5-fluorouracil (5-FU) and cisplatin for first-line (1L) treatment of advanced gastric cancer

    Yung-Jue Bang, Kei Muro, Charles S. Fuchs, Talia Golan, Ravit Geva, Hiroki Hara, et al.

    J Clin Oncol 35, 2017 (suppl; abstr 4012)

    Editorial comment from Prof Lordick & Dr Smyth:
    The results from Keynote 059 cohort 2 show that the anti PD-1 antibody pembrolizumab can be safely combined with standard cisplatin and fluoropyrimidine chemotherapy for treating patients with gastric cancer.    In this relatively small study, radiological response rates were encouraging (ORR 60%) as was overall survival (13.8 months).  Depending on the results of ongoing trials chemotherapy plus checkpoint inhibitors may also be an option for patients with advanced gastroesophageal cancer.

  • Nivolumab ± ipilimumab in pts with advanced (adv)/metastatic chemotherapyrefractory (CTx-R) gastric (G), esophageal (E), or gastroesophageal junction (GEJ) cancer: CheckMate 032 study

    Yelena Yuriy Janjigian, Patrick Alexander Ott, Emiliano Calvo, Joseph W. Kim, Paolo Antonio Ascierto, Padmanee Sharma, et al.

    J Clin Oncol 35, 2017 (suppl; abstr 4014)

    Editorial comment from Prof Lordick & Dr Smyth:
    Checkmate 032 shows that the combination of two checkpoint inhibitors with different mechanisms of action (anti-PD1 plus anti-CTLA4: Nivolumab 1mg/kg and Ipilimumab 3mg/kg every three weeks) shows promise for the treatment of advanced and pretreated gastric cancers. Response rates for PD-L1 positive gastric cancers were reported to be as high as 40% for combination therapy in PD-L1 positive patients and survival rates after 18 months of treatment in patients with PD-L1 positive tumors were as high as 50%.    Whether or not this combination will be established as a chemotherapy free option in the treatment algorithm of gastric cancer depends on the results of ongoing randomized controlled trials.

  • KEYNOTE-059 cohort 1: Efficacy and safety of pembrolizumab (pembro) monotherapy in patients with previously treated advanced gastric cancer

    Charles S. Fuchs, Toshihiko Doi, Raymond Woo-Jun Jang, Kei Muro, Taroh Satoh, Manuela Machado, et al.

    J Clin Oncol 35, 2017 (suppl; abstr 4003)

    Editorial comment from Prof Lordick & Dr Smyth:
    Keynote-059 confirms in a relatively big patient cohort, predominantly recruited in non-Asian populations, the efficacy of an anti-PD1-directed immune checkpoint therapy in advanced and pre-treated gastric cancer. Approximately every tenth patient responds to treatment. In case of a positive PD-L1-status (defined as ≥1% of cancer cells or tumor stroma cells stain positive for PD-L1) every fifth patient responds to Pembrolizumab. However, also PD-L1 negative cancers can respond. A very interesting response rate of 60% was seen in the relatively rare (4%) subgroup of patients with high microsatellite instability (MSI-H) gastric cancers.   The results of other ongoing clinical trials and decisions from regulatory authorities will determine in which lines of treatment and in which combination, if any pembrolizumab will be established in routinetreatment algorithms for gastric cancer. We hope that the authorities outside US will soon follow the good example of the FDA to register pembrolizumab for MSI-H irresectable and metastatic gastric cancer and other solid tumors.

  • Perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): ...

    Salah-Eddin Al-Batran, Nils Homann, Harald Schmalenberg, Hans-Georg Kopp, Georg Martin Haag, Kim Barbara Luley, et al.

    J Clin Oncol 35, 2017 (suppl; abstr 4004)

    Editorial comment from Prof Lordick & Dr Smyth:
    The perioperative combination chemotherapy FLOT (5-FU, Leucovorin, Oxaliplatin und Docetaxel) achieved a better progression-free and overall survival compared with ECF/ECX (Epirubicin, Cisplatin, 5-FU/Capecitabine) in patients with locally advanced operable gastric cancer or adenocarcinoma of the oesophago-gastric junction. The safety of both regimens was comparable. Perioperative complications and mortality were not increased with FLOT. In conclusion, ECF/ECX should not be used anymore. Whether patients with concomittant diseases or old patients should be treated with less intensive chemotherapy, e.g. with FLO, remains an individual decision at the current timepoint. FLOT can now be regarded as a new standard regimen in patients with locally advanced gastric cancer and adenocarcinoma of the oesophago-gastric junction.

Editor Summary:

Following ASCO 2017, the results of the FLOT4-AIO study will lead to a change in the standard of care for patients with resectable gastroesophageal cancer who are treated with perioperative chemotherapy.

For patients with advanced, unresectable or metastatic gastroesophageal cancer, checkpoint inhibitors either alone, in combination with each other, or combined with chemotherapy have shown promising results. Responses have been seen in patients with tumors which both are PD-L1 positive and negative, and more work to determine the best biomarker to select gastroesophageal cancer patients for checkpoint inhibitor therapy is required.

Professor Florian Lordick and Dr Elizabeth Smyth make a selection of their recommended abstracts in Upper GI from ASCO 2017. These include abstracts with the latest trial date including:
KEYNOTE-059 cohort 1 and KEYNOTE-059 cohort 2 trials (Pembrolizumab), the CheckMate 032 study (Nivolumab / ipilimumab) and FLOT4 (5-FU, Leucovorin, Oxaliplatin und Docetaxel) which can now be regarded as a new standard regimen in patients with locally advanced gastric cancer and adenocarcinoma of the oesophago-gastric junction. View the abstracts and further editorial insight here:

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ECCO2017 symposium webcast: Treatment evolution in advanced GI malignancies

Welcome and introduction - Florian Lordick


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