A Case of Metastatic Lung Adenocarcinoma EGFR ve, ALK +

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1 ESMO Preceptorship Programme Dr Najihah Abu Bakar University Malaya Medical Centre, Kuala Lumpur, Malaysia A Case of Metastatic Lung Adenocarcinoma EGFR ve, ALK +

2 HISTORY Mr TT/ 65yo/ Male/ Non smoker/no comorbidities Dx : Metastatic lung cancer with bone and nodal metastases Presented with knee pain and backache in December 2013 Staging CT TAP Dec 2013 : lung nodules with mediastinal lymphadenopathy and multiple spinal metastatic lesions with compression fracture L3 and narrowing of spinal canal Biopsy of vertebrae lesion : metastatic adenocarcinoma of lung, TTF-1, CK7 + CK20 and PSA negative EGFR wild type, ALK 98% positive

3 Crizotinib Ceritinib Jan Feb Jun Sep Palliative RT to T11-L4 20Gy/5# T Crizotinib 250mg BD (self-purchased) CT TAP mediastinal disease stable. Improved lung disease. Bone evidence of increased volume in the lower lumbar metastasis Radiologist impression : Progression in bone Oncologist impression : Stable disease In view of findings, application for Ceritinib done. Worried about his bone disease. Free access programme, started on T Ceritinib from 300mg 450mg 600mg Experienced diarrhoea, abdominal discomfort and weight loss of 2 kg within 2 weeks

4 Crizotinib Ceritinib Crizotinib Oct Nov Dec Feb 2015 Switched back to Crizotinib 250mg BD due to poor tolerability While in India to buy Crizotinib, PET CT done: same changes except 2 brain lesion is not PET avid. New PET avid mediastinal nodes. Brain lesions : cystic - looking Applied Crizotinib in reimbursement drug programme (government) Free access programme T Ceritinib 300mg BD Main symptom : stiffness in spine and jaw pain CT Brain, TAP (no prior CT Brain) -Multiple lesion in left cerebellum, frontal and parietal -Stable bone, nodal metastases

5 Crizotinib Ceritinib Crizotinib Jun 2015 Ceritinib CT Brain, TAP : Stable lung, bone and nodal disease. Bigger brain lesion but not increased in number MRI Brain : 2 new lesions likely progression from previous nonconspicuous lesion MDT discussion for biopsy TRO infection as lesions are cystic looking Brain biopsy : Adenocarcinoma No neurology symptoms Ceritinib increased to 600mg BD Complicated with ONJ on antibiotic Dec 2015 Free access programme ended. Loss of appetite G2, weight loss G3 on Ceritinib Reimbursement drug programme approved. Changed back to Crizotinib 250mg BD CT TAP: Stable left lung lesions, others stable.

6 Crizotinib Ceritinib Crizotinib Ceritinib Crizotinib Jan Apr 2016 May 2016 Feb 2017 MRI Brain: Mixed response to treatment with possible skull metastasis CT TAP : Smaller left lung lesions with stable bone lesions MRI brain and whole spine : progression of intracranial disease WBRT 20Gy/5# c/o low back pain with numbness radiating down right leg to right feet CT TAP : stable disease MRI Brain :?progression in right frontal lesion Started on Dexamethasone, PPI Applied for Alectinib

7 Crizotinib Ceritinib Crizotinib Ceritinib Crizotinib Alectinib Mar - Jun 2017 Tapering dose Dexamethasone Improvement in low back pain Jul 2017 Started on Alectinib 600mg BD CT Brain and TAP: Stable mediastinal lymphadenopathies and bone metastasis. Multiple brain and leptomeningeal metastases. The left cerebellar and parasaggital lesions are larger. Oct 2017 CT TAP Stable mediastinal LN and bone metastases. Smaller and resolving brain and leptomeningeal metastasis with 2 new lesions mixed response

8 Feb 2015 (CT brain) May 2015 (CT Brain) Brain Images June 2015 (MRI brain) May 2016 (MRI brain) July 2017 (CT brain) Feb 2015

9 Topics for Discussion If he progress further, what is the recommendation? If chemotherapy, Alimta vs Vinorelbine? Brain imaging is only done if he is symptomatic, what is the recommendation for metastatic lung cancer? PDL-1 status? Should we check?

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