ESMO Consensus Conference: Interactive Session on Colorectal Cancer Guidelines A clinical case presentation on advanced colon cancer (first and second.

ESMO Consensus Conference: Interactive Session on Colorectal Cancer Guidelines

A clinical case presentation on advanced colon cancer (first and second line therapy)

Alexander SteinUniversity Cancer Center Hamburg, Germany

Disclosure

• Honoraria from Roche and Merck

Case presentation

• male, 64 years of age, ECOG 0• no relevant comorbidity• routine abdominal ultrasound revealed suspicious

liver lesions• CT chest/abdomen– 3 liver lesions up to 2.5cm– 3 suspicious pulmonary lesions up to 1cm– single bone lesion 1.8cm mixed osteoplastic/osteolytic

(left os ileum) – thickening of colonic wall (descendens)

Case presentation

• colonoscopy: non obstructive tumor without bleeding signs colon descendens– histology: adenocarcinoma

• CEA value 245 ng/ml

colon carcinoma with synchronous liver and lung metastates and potential bone involvement

Further diagnostics

• PET scan liver and lung lesions positive, bone lesion negative

• bone scan weakly positive• determination of KRAS status wildtype

ESMO consensus guidelines for management of patients with colon and rectal cancer 2012.

KRAS mutation precludes efficacy of treatment with anti-EGFR antibodies and KRAS status determination is therefore mandatory before treatment [I, A].

1. start pure palliative chemotherapy for metastatic disease

2. discuss patient within MDT according to clinical presentation and determine treatment aim and clinical grouping

Acc. to ESMO guidelines next step should be ...

Definition of treatment strategy

The optimal strategy should be developed according to the characteristics of the patient and be discussed in the multidisciplinary team and should incorporate the (potential) view of the patient as well.

Patients can be individually divided into the 4 clinical groups, by parameters describing localization, extent, and resectability of the disease, tumour dynamics, co-morbidity, potential of the patient to tolerate chemotherapy and secondary surgical treatment [IV, B].

group clinical presentation treatment aim treatment intensity

0 clearly R0-resectable liver and/or lung metastases cure, decrease risk of relapse

nothing or moderate (FOLFOX)

1 liver and/or lung metastases only

whichmight become resectable after induction chemotherapy±limited/localized metastases to other sites, e.g. locoregional lymphnodesphysically able to undergo major surgery (biological age, heart/lung condition)

maximum tumour shrinkage

upfront most active combination regimen

2 multiple metastases/sites, with

rapid progression and/or tumour-related symptoms/risk of rapid deterioration co-morbidity allows intensive treatment

clinically relevant tumour shrinkage as soon as possible

at least achieve control of progressive disease

upfront active combination: at least doublet

3 multiple metastases/sites, with never option for resection and/or no major symptoms or risk of rapid

deterioration and/or severe comorbidity (excluding from later

surgery and/or intensive systemic treatment, as for groups 1+2)

abrogation of further progression

tumour shrinkage less relevant

low toxicity most relevant

treatment selection according to disease characteristics and patients preference re toxicity and efficacy: “watchful waiting”sequential approach: start with osingle agent, or odoublet with low toxicityexceptional triplets

Clinical groups for first line treatment stratification

Clinical course

• Patient was considered potentially curative (group 1) by MDT despite the unclear single bone lesion.

Acc. to ESMO guidelines primary tumor should be managed by ...

1. resection of primary tumor before chemotherapy2. upfront chemotherapy and delayed resection in

case of major response (but still unresectable mets)3. upfront chemotherapy and resection only in case of

local symptoms

Clinical course

• primary tumor was left in situ

Potentially resectable metastatic disease after chemotherapy (group 1)For initially unresectable metastatic disease, most active available induction treatment should be chosen [V, C]. If metastases become resectable surgery for primary and metastases should be performed.Palliative surgery, stenting, laser ablation, or (chemo)radiation in case of unresectable disease, even after systemic treatment should be confined to bleeding or obstruction and as minimal invasive as possible and non invasive measures applied first [V, C].

6 months postop FOLFOX

3 months postop FOLFOX

synchronous metastatic colon cancer with intact primary

unresectable metastases

3 months preop FOLFOX

R0/R1 resectable metastases

yes no

surgery of primary: individual decision (e.g. complications or

emergency)

intensive upfront chemotherapy

continue initial treatment for a

total of 6 months

yes no

continue chemotherapy

resectability achieved?

resectability achieved?

resection of primary and metastases (simultaneous or delayed)

single, <2cmliver met

Treatment algorithm for synchronous metastatic colon cancer

• FOLFOX + bevacizumab• restaging after 2/4 months: partial response (RECIST)• restaging after 6 months (PET/CT):

– liver mets: one remaining with 1.4cm (PET positive)– lung lesions: complete response– bone lesion: unchanged– colonoscopy witout macroscopic evidence of residual primary

tumor, biopsy negative (local CR)– decreased tolerability with peripheral neuropathy G2 and

asthenia G1

Clinical course

Clinical course

major response liver and complete response lung-metastases and primary tumor

• Decision was made by MDT to classify the patient as potentially curative based on age, ECOG, major response and unchanged bone lesion. However, resection or RFA of remaining central liver met. seemed technically difficult.

Further management?

1. maintenance (5FU/Cape and/or bevacizumab)2. complete stop of treatment3. consider locally ablative procedure

• helical tomotherapy with 10x 4Gy for liver metastasis and as a precaution for the bone lesion

• followed by complete stop of treatment

If metastases are not resectable due to their location additional measures like radiofrequency ablation or stereotactic body radiotherapy (in specialized institutions) should be considered, although the benefit is not formally proven [III, B].

Clinical course

• no evidence of disease for 10 months, followed by progressive disease with 4 new liver and disseminated pulmonary lesions, single bone lesion unchanged

• remaining toxicity: PNP G1 (12 months after last oxaliplatin administration)

Acc. to ESMO guidelines further treatment should be ...

1. restart FOLFOX + bevacizumab2. change to irinotecan based second line (FOLFIRI +/-

targeted agent)

Reinduction

• reinduction FOLFOX + bevacizumab

In first line treatment patients should be treated as long as possible by restart of the former first line regimen (reinduction), when the toxicity (especially neurotoxicity) allows such reinduction.

• restaging after 2 months: stable disease• restaging after 4 months: progressive disease

(multiple new liver lesions)

Further treatment?

1. FOLFIRI + panitumumab2. FOLFIRI/irinotecan + cetuximab3. FOLFIRI + bevacizumab (beyond progression - TML)4. FOLFIRI5. single agent EGFR antibody

Course of second line

• FOLFIRI + panitumumab• restaging after 3 months: stable disease (SLD -25%),

dose reduction FOLFIRI 80% due to neutropenia• restaging after 6 months: partial response (SLD -8%)• side effects: asthenia G2, cutaneous tox. G1

Thank you