ESMO Preceptorship Programme

Presentation of three challenging clinical cases and Faculty discussion

Andrés Cervantes/Dirk Arnold

Colorectal Cancer – Valencia – 12,13 May 2017

ESMO PRECEPTORSHIP PROGRAM

Disclosures

Consulting and advisory services, speaking or writing engagements,

public presenations:

Servier, Merck Serono, Amgen, Roche, Lilly, Bayer, Novartiis, Takeda, Beigene

Direct research support to the responsible project lead:

Servier, Roche, Genentech, Bayer, Janssen, Merck Serono, Medimmune

2

• 62 year old male

• No previous diseases or comorbidities

• Constipation and rectal bleeding

• False diarrhea and tenesmus

• No weight loss

• PS 1

CLINICAL CASE

3

• No peripheral lymph nodes

• No hepatomegaly

• No ascites

• No pleural effusion

• DRE: Fixed tumor at 3 cm from the anal

verge involving 3/4 of the circumference

Physical examination

4

• Rigid rectoscopy: a fixed tumor at 3 cm from the

anal verge obstructing ¾ of the circumference

• Biopsy: poorly differentiated invasive

adenocarcinoma of the rectum

• Colonoscopy: Tumor at 5 cm. Flexible colonoscopy

able to surpass the rectal mass reaching the cecum.

No synchronous polyps.

Diagnostic tests-1

5

• CBC: no anemia

• Biochemistry: within normal range. No liver

alterations.

• CEA: 12.9 ng/ml

• Thorax CT scan: No lung mets

• Abdomino-pelvic CT-scan: 9 liver

metastatic nodes involving both liver lobes

Diagnostic tests-2

6

Abdominal CT-scan

7

• MRI Staging

• MDT discussion

• Preoperative chemoradiation if indicated

• TME Surgical resection

• Pathology assessment and estimation of risk

• Postoperative chemotherapy if indicated

Current approach to localized rectal cancer

8

Magnetic resonance imaging

9

Magnetic resonance imaging

10

• Bulky rectal tumor below the levators and located at 1 cm from the anal verge

• Several nodes with suspected neoplastic involvementand tumor involving the mesorectal fascia

• Invasion by tumor of mesorectal fascia at the anterior and lateral left side

• Left puborectal muscle involved

• No prostatic involvement, but very close to Denonvilliers fascia

• No extramural vascular invasion

• No lateral pelvic nodes (extramesorectal)

Magnetic resonance imaging report

11

• Symptomatic locally advanced rectal cancer

• 62-year old male

• Extensive and unresectable liver only

metastatic disease

• All RAS and BRAF wild-type

• Fit patient without comorbidities

• Do not miss any opportunities

SUMMARY

12

1. Chemoradiation followed by CT

2. Chemotherapy + anti-EGFRs only

3. 5x5 Radiation followed by Chemo

4. TME up front plus Chemo

5. Liver resection plus chemoradiation

Your treatment plan:

13

• Chemoradiation followed by CT

• Chemotherapy + anti-EGFRs only

• 5x5 Radiation followed by Chemo

• TME up front plus Chemo

• Liver resection plus chemoradiation

Your treatment plan:

14

• MRI Staging

• MDT discussion

• Preoperative chemoradiation or 5x5

radiation if indicated

• TME Surgical resection

• Pathology assessment and estimation of risk

• Postoperative chemotherapy if indicated

Current approach to localized rectal cancer

15

• Radiation 5x5 Gy was given for

symptomatic purposes

• Chemotherapy was started two weeks later

within a randomized phase II trial with

FOLFOX-Bev +/- experimental agent

• Assessment of response was considered 8

weeks after starting FOLFOX-Bev

Treatment plan

16

Assessment of primary tumor by

Magnetic Resonance Imaging

• Asymptomatic

• Disappearance of all previous symptoms

• DRE: no mucosal damage

• Rigid rectoscopy: Normal appearance

with no residual ulcer or scar

• Endoscopic ultrasonography: no

disruption of bowel layers

17

Assessment of primary tumor

18

Assessment of liver mets by

CT-scan

19

1. Liver surgery followed by TME

2. TME followed by liver surgery

3. Liver surgery and surveillance for the

primary rectal tumor

4. No further therapy and reintroduce

treatment upon progression

Your treatment plan:

20

• Liver surgery followed by TME

• TME followed by liver surgery

• Liver surgery and surveillance for the

primary rectal tumor

• No further therapy and reintroduce

treatment upon progression

Your treatment plan:

21

• Liver surgery was planned after 8 courses of

FOLFOX-Bev plus 4 courses FULV-Bev

• A right hepatectomy after right hepatic

artery embolization was performed 6 weeks

after the last dose of Bevacizumab

• Surveillance and follow up for the primary

rectal tumor

• No postoperative ChT was considered

Treatment plan

22

• Hospitalized for 7 days

• No liver damage: steatosis, steatonecrosis or

sinusoidal occlusive disease

• A pCR was defined in the pathology report

• Multiple scar areas with no rest of

malignant cells

Assessment of liver surgery

23

• Rectal exam plus proctoscopy plus MRI

every 4 months

• CT-scan every three months

• No evidence of progression 20 months after

diagnosis

Follow up plan

24

• Locally advanced rectal cancer with synchronous multiple liver only metastatic disease

• Multidisciplinary discussion essential for all rectal cancer cases: at start and during treatment or follow up

• Do not miss any opportunities for your patients

• 5x5 Radiation plus CT may induce clinical CRs

• After chemotherapy, liver resection recommended if mets become resectable

• Surveillance of the primary tumor as an emerging option

• So far successful multimodality treatment

CONCLUSIONS

MULTIDISCIPLINARY TEAM FOR

COLORECTAL CANCERBIOMEDICAL RESEARCH INSTITUTE INCLIVA

UNIVERSITY HOSPITAL VALENCIA

• MRI: Salvador Campos

• Pathology: Samuel Navarro, Carolina Martínez

• Surgery: Alejandro Espí, Estephanie García-Botello,

Vicente Plá, David Moro, José Martín Arévalo.

• Radiation Oncology: Esther Jordá

• Medical Oncology: Susana Roselló, Desamparados Roda,

Marisol Huerta, Isabel Chirivella (Family Cancer Unit),

Ricard Borras, Alba Viala, Federica Papaccio, Angelica

Petrillo, Andrés Cervantes

26

• Woman 33 years old.

• Pregnacy in the 17th week.

• Complains about rectal bleeding and

hypertransaminasemia.

• Abdominal-pelvic MRI: Multiple liver metastasis.

Thickening of sigma.

• CEA 82 ng/mL

• LDH 2450 IU/ml AlK Ph 285 IU/ml

• Colonoscopy: Tumor at 25 cm of anal margin.

Biopsy����Adenocarcinoma. RAS/BRAF wt.

CLINICAL CASE

MARCH 2015

Abdominal CT-scan

28

1. Surgery for the primary followed by CT

2. FOLFOX or FOLFIRI + anti-EGFRs

3. FOLFOXIRI + BEV

4. Cape plus Bev

5. FOLFIRI or FOLFIRI +BEV

Your treatment plan:

02/15

Diag.

Abortion

03/15

FOLFOXIRI-BEVA

08/15

8 cycles

PR(-50%)

Non resect.

->

FOLFIRI-

Beva.

Evolution and treatmentsDISEASE EVOLUTION AND

TREATMENT

MARCH 2015 AUGUST 2015

RESPONSE ASSESSMENT: PR

Evolution and treatments

02/15

Diag.

Abortion

03/15

FOLFOXI

RI-BEVA

08/15

8 cycles

PR(-50%)

Unresect.

->

FOLFIRI-

Beva.

01/16

6 cycles

PR maint.

Haematological

tox.

H. And F. Sind.

Diarreha.

03/16

10 cycles

PR maint.

->5-FU-Beva.

????

DISEASE EVOLUTION AND

TREATMENT

AUGUST 2015 JULY 2016

RESPONSE ASSESSMENT: PD

33

1. REINTRODUCE FOLFOX + BEV

2. FOLFIRI + anti-EGFRs

3. FOLFOX + BEV

4. IRINOTECAN + anti-EGFRs

5. FOLFIRI or FOLFIRI +BEV

Your treatment plan:

AUGUST 2015 JULY 2016

RESPONSE ASSESSMENT: PD

Evolution and treatments

02/15

Diag.

Abortion

03/15

FOLFOXI

RI-BEVA

08/15

8 cycles

PR(-50%)

Unresect.

->

FOLFIRI-

Beva.

01/16

6 cycles

PR maint.

Haematological

tox.

H. And F. Sind.

Diarreha.

03/16

10 cycles

PR maint.

->5-FU-Beva.

07/16

8 cycles

Liver PD

->FOLFOX-Beva.

DISEASE EVOLUTION AND

TREATMENT

JANUARY 2017

• 11 cycles of FOLFOX-Bevacizumab.

• In CT scan no evidence of progression: increase of 20%

of metastasic lesions.

• LIVER PROGRESSIVE DISEASE

• Blood test:

– Hypertransaminasemia.

– LDH 1006 U/ml. ALP 321mU/ml.

– CEA 180 ng/ml (previous 93,7 ng/ml).

DISEASE EVOLUTION AND

TREATMENT

37

1. REINTRODUCE FOLFIR + BEV

2. FOLFIRI + anti-EGFRs

3. CAPE + BEV

4. IRINOTECAN + anti-EGFRs

5. BEST SUPPORTIVE CARE

Your treatment plan:

Evolution and treatments

02/15

Diag.

Abortion

03/15

FOLFOXI

RI-BEVA

08/15

8 cycles

PR(-50%)

Unresect.

->

FOLFIRI-

Beva.

01/16

6 cycles

PR maint.

Haematological

tox.

H. And F. Sind.

Diarreha.

03/16

10 cycles

PR maint.

->5-FU-Beva.

07/16

8 cycles

Liver PD

->FOLFOX-

Beva.

11/16

8 cycles

SD

01/17

11 cycles

Liver PD

->CPT11-cetuximab

03/17

4 cycles

PR (-50%

liver met.)

JANUARY 2017 MARCH 2017

DISEASE EVOLUTION AND

TREATMENT

Evolution and treatments

02/15

Diag.

Abortion

03/15

FOLFOXI

RI-BEVA

08/15

8 cycles

PR(-50%)

Non resect.

->

FOLFIRI-

Beva.

10/15

3 cycles

PR

maintenance

01/16

6 cycles

PR maint.

Haematological

tox.

H. And F. Sind.

03/16

10 cycles

PR

->5-FU-Beva.

07/16

8 cycles

Liver DP

->FOLFOX-

Beva.

11/16

8 cycles

SD

01/17

11 cycles

Liver DP

->CPT11-

cetuximab

03/17

4 cycles

PR (-50%

liver met.)

05/17

8 cycles

PR maint.

1. REGORAFENIB

2. LONSURF

3. CAPE + BEV

4. TEST HER2 STATUS

5. BEST SUPPORTIVE CARE

OPTIONS FOR FUTURE

TREATMENTS

• Herceptest� Positive 3+.

OPTIONS FOR FUTURE

TREATMENTS

Kavuri SM et al, Cancer Discovery 2015; 5:832-841

Anomalías moleculares de HER2 en cáncer de colon

Kavuri SM et al, Cancer Discovery 2015; 5:832-841

Anomalías moleculares de HER2 en cáncer de

colon: Sesibilidad a Lapatinib + Trastuzumab

HERACLES treatment and assessments

Siena et al Lancet Oncol, 2016; 17:438-446.

Lapatinib/Trastuzumab en cáncer de colon HER2+++Estudio Heracles