LOCALLY ADVANCED OESOPHAGOGASTRIC …...but new 3 lesions in both lungs CT scan May 2018 2 lesions mets? in progression– accesible for histological verification VATS June 2018- adenocarcinoma

LOCALLY ADVANCEDOESOPHAGOGASTRIC JUNCTIONCANCER

Radka Obermannova,MD,PhD

Masaryk Memorial Cancer Institute, Brno, Czech Republic

DISCLOSURE OF INTEREST

Grant/Research Support: Czech Health Research Council, Merck

Consultant: Servier, Sotio, Merck

Speaker’s Bureau: Eli Lilly, BMS, Merck, Roche

Radka Obermannova, MMCI

ONSET 2016- PATIENT CHARACTERISTICS

43 years old male patient No family history No medical history, only bipolar disorder currently asymptomatic PS1 No smoking, no alcohol, Lawyer, marathon runner, married, 2 children


ONSET 2016- DISEASE CHARACTERISTICS

Difficulties of swallowing

Weight loss 6kg/4months

Tiredness

Anorexia

At the time of diagnosis: height 176cm, weight 66 kg, BMI 21.3Radka Obermannova, MMCI

Onset 2016- Patient characteristicsQ1:Diagnostics in gastric/OGJ cancer

Standard investigations? Endoscopic ultrasound (EUS) CT or PET/CT All of above Exploratory laparoscopy No additional investigations


Endoscopy: Siewert II tumour, adenocarcinoma G3, HER 2 negative


SIEWERT CLASSIFICATION

Radka Obermannova, MMCIMariette C et al. Lancet 2011Schneider PM et al. Springer Cham 2017


DIAGNOSIS NOVEMBER 2016

Endoscopy: Siewert II tumourHistology: adenocarcinoma G3HER2 negativeEndoscopic ultrasound: cT3N2M0PET/CT scan: no metastases


Operable OGJ cancercT3N2(PET/CT)M0, stage IIIB

Onset 2016- Patient characteristicsOnset 2016- Patient characteristicsQ2: NEXT STEPS?

Perioperative chemotherapy

Neoadjuvat chemoradiotherapy

Upfront surgery, adjuvant chemotherapy

Upfront surgery/adjuvant chemoradiotherapy


ESMO OESOPHAGEAL CANCER GUIDELINES

Radka Obermannova, MMCI Lordick et al. Ann Oncol 2016 Sep;27(suppl 5):v50-v57

Q3: NEXT STEPS- PERIOPERATIVE TREATMENT

3 cycles of ECF 2-6/2016Side effects: vomitus G1, neuropathy G2, weight lossEffect: Clinically: weight loss, symptoms withdrawalCT: SD according to RECISTSurgery July 2016:


Perioperative TherapyUK MAGIC 2006

ECF

Surgery alone

Stomach Cancer 74%EGJ +DE Cancer 26%

5-y-OS36%vs23%

Cunningham D et al. N Engl J Med 2006;355:11-20Ychou M et al .J Clin Oncol 2011;29:1715-1721

French FNCLCC 2011

Stomach Cancer 25%EGJ+DE Cancer 75%5-y-OS 38%vs24%

Surgery alone

5-FU

PERIOPERATIVE TREATMENT /REGIMENS/

Dublets: 5-FU/cisplatin or FOLFOX Triplets ECF was substituted by FLOT or modifications with docetaxel in fit

patients or non- elderly


French FNCLCC 2011 AIO-FLOT

PERIOPERATIVE TREATMENT /REGIMENS/

Dublets: 5-FU/cisplatin or FOLFOX Triplets ECF was substituted by FLOT or modifications with docetaxel in fit

patients or non- elderly

Ychou M et al .J Clin Oncol 2011;29:1715-1721


French FNCLCC 2011 AIO-FLOT

ECF/ECX FLOT

mOS 35 months 50 months [27-46] [38-na]

HR 0.77 [0.63 - 0.94] p=0.012 (log rank)

2y 59% 68% 3y 48% 57% 5y 36%

45%

OS rate* ECF/ECX FLOT

Al-Batran et al. ASCO 2017; abstract 4006

Onset 2016 Patient characteristicsOQ3: Next steps- postoperative treatment?nset 2016- Patient characteristics


Transthoracal OesophagectomyAdenocarcinoma G3, ypT3N2(6/15LN)M0, Mandard TRG 4, HER2negative

Treatment standard – postoperative chemotherapy

Q3: NEXT STEPS- POSTOPERATIVE TREATMENT?


Smyth L et al, J Clin Oncol 2016 Aug 10;34(23):2721-7Treatment standard – postoperative chemotherapy

Q3: NEXT STEPS- POSTOPERATIVE TREATMENT?


CRITICS(NL, Sweden)Stage Ib-IVa

RCTx (ECX)

CTx (ECX)

Resection

Resection

Radio-CTx

CTx (ECX)

Cats A et al.Lancet Oncol 2018; 19: 616–28

Q3: Next steps- postoperative treatmentVESTIGE STUDY

Lordick F et al, EORTC GI Group 2017

EORTC 1707 (start 2019)DESIGN

POSTOPERATIVE TREATMENT

3 cycles of ECF by June 2017

….according to treatment standard

Side effects: vomitus G1, neuropathy G2,

After chemotherapy patient clinical conditions were PS 1, weight loss 16 kg, no symptoms


ONSET 2016- PATIENT CHARACTERISTICSDISEASE RELAPSE …… OCTOBER 2017(3 MONTHS AFTER COMPLETION OF POSTOPERATIVE CHEMOTHERAPY ECF)

PS1, weight 61kg,asymptomatic

PET/CT: 2 lung lesions 8-10mm in diameter, mets suspected

Reffered to our center for trial treatment with PD-L1


Q3:NEXT STEPS: OPERABLE 2 NEW LUNG LESIONS IN BOTH LUNGS

Palliative chemotherapy Surgery because of operable

lesions and unclear etiology WW strategy and CT in 2 or 3

months Other options?Local methods- STX? Radiofrequencyablation?


Disease recurrence 3months after completion of primary treatment

CT scan January 2018Complete remission of descibed 2 lesions but new 3 lesions in both lungsCT scan May 2018 2 lesions mets? in progression– accesible for histological verificationVATS June 2018- adenocarcinoma G2, HER2 amplification, PD-L1 negative, pMMRRadka Obermannova, MMCI

NEXT INVESTIGATIONS

CENTRAL VALIDATION OF HER2 IN GASTRIC CANCER: HIGH HETEROGENEITY IN HER2 EXPRESSION AND ITS IMPACT ON SURVIVAL

Haffner I, IGCC 2019Courtesy Florian Lordick

SINCE AUGUST 2018 SYSTEMIC TREATMENT- FIRST LINERESTAGING- CT SCANS

partial remissioncomplete remission

Treatment stop because of toxicity-neurotoxicity, relaps of bipolar symptoms (brain MRI without pathology), PS2

First line: August 2018- June 2019Trastuzumab/5-fluorouracil/folinicacid/cisplatin……trastuzumab/5-FU/folinic acid




First line: August 2018- June 2019Trastuzumab/5-fluorouracil/folinicacid/cisplatin……trastuzumab/5-FU/folinic acid




First line: August 2018- June 2019Trastuzumab/5-fluorouracil/folinicacid/cisplatin……trastuzumab/5-FU/folinic acid,August 2019 clinically stable, next CT planned inSeptember 2019

DISEASE PROGRESSION? Back to first line with trastu

Ramucirumab/paclitaxel

Ramucirumab

Chemotherapy (irinotecan, docetaxel, paclitaxel,

FOLFIRI)



SECOND LINE

Annals of Oncology, Volume 30, Issue 1, January 2019, Pages 19–33, https://doi.org/10.1093/annonc/mdy502

Second line:?


THANK YOU FOR YOUR ATTENTION.

1935 MMCI 2019

Neoadjuvant Therapy

31

RANDOM

Primary Endpoint:OS3-years-OS-Rate55% CROSS vs. 68% FLOT

N=438

Stadium II Stadium III

Neoadjuvant Radio-CTX – CROSS RegimenRESECTION

Neoadjuvant Chemo-Tx: FLOT RegimenRESECTION

Hoeppner J et al. BMC Cancer. 2016 Jul 19;16:503.

Perioperative TherapyUK MAGIC 2006

ECF

Surgery alone

Stomach Cancer 74%EGJ +DE Cancer 26%

5-y-OS36%vs23%

Cunningham D et al. N Engl J Med 2006;355:11-20Ychou M et al .J Clin Oncol 2011;29:1715-1721

French FNCLCC 2011


Surgery alone

5-FU

Perioperative Treatment for Localized Gastric Cancer AIO-FLOT

Overall Survival

ECF/ECX FLOT

mOS 35 months 50 months [27-46] [38-na]

HR 0.77 [0.63 - 0.94] p=0.012 (log rank)

2y 59% 68% 3y 48% 57% 5y 36% 45%

OS rate* ECF/ECX FLOT

*projected OS rates

Al-Batran et al. ASCO 2017; abstract 4006

MSI-H Gastric Cancer – Postoperative Chemotherapy

Kim SY et al. Int. J. Cancer 2015; 137: 819–825

LOCALLY ADVANCED OESOPHAGOGASTRIC …...but new 3 lesions in both lungs CT scan May 2018 2 lesions mets? in progression– accesible for histological verification VATS June 2018- adenocarcinoma

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