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ESMO Preceptorship Programme
A Myth becoming a Reality… Long survival in metastatic NSCLC
EL DAKDOUKI Yolla, MD
Clinical research Fellow
Department of Medical Oncology, Gustave Roussy Cancer Institute
Villejuif, France
Lung Cancer – Manchester, UK – 01-03/03/2017
ESMO PRECEPTORSHIP PROGRAM
Diagnostic
65 years female patient, Asian, non-smoker
Past medical history:
HTN, osteoporosis
1st symptom:
- Right thoracic pain in summer 2012
Whole Body CT-scan, PET Scan and cerebral MRI in July 2012:
- Lung mass in the right lower lobe with multiple nodules in the right
lung
- Right pleural effusion
- No extra thoracic metastasis
ESMO PRECEPTORSHIP PROGRAM
Biopsy: Adenocarcinoma TTF1+ CK7+ CK20 –
Molecular profile: EGFR Exon 19
deletion of 15 bp (found later)
Staging: cT4N0M1a stage IV
Treatment ??
Diagnostic Management
for NSCLC (Before the Molecular Profile results)
ESMO PRECEPTORSHIP PROGRAM
Carboplatin- Paclitaxel- Bevacizumab x 6 cycles
Carboplatin because of Creatinine Clearance -Cockroft-
49 mL/min
CT scan post C6: Disappearance of the right pleural
effusion and lung nodules, peristance of one sub-
pleural micronodule of 5 mm
Maintenance with Beva 7.5 mg/kg/3weeks
(7 cycles from 02/01/2013 to 15/05/2013)
CT scan 25/05/2013: lung PD
1st line platinum-based Chemo
Therapeutic strategy for advanced
non-squamous NSCLC
D1 13/08/2012
10 months
PD on 25/05/2013
ESMO PRECEPTORSHIP PROGRAM
Erlotinib 150 mg/d
Toxicity: Grade 1 skin rash treated with oral
Doxycycline
PR
PD on May 2014 (infracentrimetric lung and pleural
nodules)
Pemetrexed x 6 cycles
November 2014: - Pleural and pulmonary PD,
- New hepatic lesions
- New cerebral lesion of 4 mm
3rd line Chemo with Pemetrexed
Therapeutic strategy for advanced
non-squamous NSCLC
D1 23/05/2014
5 months
2nd line: Targeted Therapy D1 04/06/2013
12 months
ESMO PRECEPTORSHIP PROGRAM
ERLOTINIB 6 months
- Clinical response
- Radiological PR
- Good tolerability (rash, diarrhea G1)
4th line : Rechallenge EGFR TKI
Therapeutic strategy for advanced
EGFRmut+ NSCLC
PLEURAL AND METASTATIC
PROGRESSION
March 2015
6 months
PD after 6 months with TKI treatment
D1 10/11/2014
Patient was referred to our center 32 months after 1st diagnosis
ESMO PRECEPTORSHIP PROGRAM
Summary (I) 65 years female patient
Advanced lung adenocarcinoma cT4N0M1a stage IV
Progressive disease after 4 lines of therapy:
Unknown molecular status
EGFR mutation exon 19 del
1st line platinum-based Chemo then maintenance with Beva
2nd line: Targeted Therapy with Erlotinib
10 months
12 months
3rd line: Pemetrexed
4th line: Targeted Therapy with Erlotinib
5 months
6 months
ESMO PRECEPTORSHIP PROGRAM
PACLITAXEL 80mg/m2 d1 d8 d15
+ BEVACIZUMAB 7.5mg/kg d1
- Clinical & radiological stable disease
- Good tolerability
BEVACIZUMAB maintenance
5th line
Therapeutic strategy for advanced
EGFRmut+ NSCLC
April 2015
Nov. 2015
7 months
Aug. 2015
Lung, liver and brain PD
ESMO PRECEPTORSHIP PROGRAM
Summary (II)
65 years female patient
Advanced lung adenocarcinoma EGFRmut+ exon 19 del
Progressive disease after 3 lines of chemotherapy & 1 line of TKI
Resistance mutation?
Re-BIOPSY
(Lung and ctDNA)
- EGFR mutation exon 19 del
- T790M mutation
Next Generation Targeted therapy
Oxnard CCR 2011
ESMO PRECEPTORSHIP PROGRAM
OSIMERTINIB x 12 months
- Clinical response
- Radiological partial response
(Complete hepatic response)
- Good tolerability (rash G1)
Stereotaxic Radiation Therapy
- Brain metastasis (x3)
6th line
Therapeutic strategy for advanced
EGFRmut+ NSCLC
Nov. 2015 Scan baseline
06/11/15
After 1 month
of AZD
04/01/16
ESMO PRECEPTORSHIP PROGRAM
Summary (III)
65 years female patient, Asiatic, non-smoker
Advanced lung adenocarcinoma EGFRmut+ exon 19 del
PD (pleura and lung) after 3 lines of CT & 2 lines of TKI
PD-L1 status?
IHC
(Ab Clone 28-8)
PD-L1 30% positive
Immune checkpoint inhibitors
ESMO PRECEPTORSHIP PROGRAM
NIVOLUMAB
- Clinically stable & good tolerability
- Radiological evaluation planned after 12 weeks
7th line
Therapeutic strategy for advanced
EGFRmut+ NSCLC
Nov. 2016
ESMO PRECEPTORSHIP PROGRAM
Summary (IV)
65 yo female patients with advanced lung adenocarcinoma
Molecular profile: EGFR mutation exon 19 del + T790M positive
PD-L1 expression: 30% positive
1st line
3rd line
4th line
5th line
6th line
7th line
Platinum CT x 6 cycles
Pemetrexed x 6 cycles
Erlotinib x 6 months
Paclitaxel-Beva x 8 months
Osimertinib x 12 months
Nivolumab (ongoing)
Mo
re th
an
3 y
ears
of s
urv
iva
l
2nd line Erlotinib x 12 months
ESMO PRECEPTORSHIP PROGRAM
What’s next?
3 lines of chemotherapy
2 lines of 1st generation TKI (including rechallenge)
1 line of next-generation TKI (for T790M+ disease)
1 line of immunotherapy in PDL1+ disease
No WBRT on brain mets
High QOL
ESMO PRECEPTORSHIP PROGRAM
ACKNOWLEDGEMENTS
Prof. Benjamin Besse
Dr. David Planchard
Dr. Laura Mezquita
Thoracic Oncology Group
Medical Oncology Department
Gustave Roussy, Villejuif, France
ESMO PRECEPTORSHIP PROGRAM
Thank You
Questions?
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