CASO CLINICO
L’inquadramento e la valutazione per la prima linea di trattamento nell’adenocarcinoma polmonare
metastatico con PD-L1 del 42%
Ilaria Attili
Istituto Oncologico Veneto Oncologia Medica 2 [email protected]
Tutor: Nicola Normanno INT Fondazione Pascale
A.Z. 57 years
• Never smoker, ECOG PS1
• Atrial fibrillation, pulmonary emphysema
• Normal laboratory findings
• December 2015: clinical onset with cough and pyrexia
Clinical examination: normal findings
Chest X ray: Ø 3 cm left superior lobe lesion
A.Z. 57 years
Contrast-enhanced CT of thorax and abdomen : Ø 31mm left superior lobe lesion, multiple left lung nodes, mediastinal lymph nodes, liver metastases
LG AIOM 2016
A.Z. 57 years
LG AIOM 2016
Novello S, Ann Oncol 2016
Complete clinical history and lab findings
Contrast-enhanced CT scan of the chest and upper abdomen
CNS imaging if neurological signs or symptoms are present
Bone imaging if metastasis are suspected
PET scan if surgery is considered
Cytological or histological sample obtained (bronchoscopy vs CT-
guided needle aspiration)
A.Z. 57 years
Bronchial biopsy
Pathology report – essential elements
• Morphology
• Essential IHC (differential diagnosis)
• Molecular analysis
• PD-L1
Tsao AS, J Thorac Oncol. 2016
Molecular analysis – essential elements
• EGFR • ALK
Study Drugs Results
IPASS Gefitinib vs
carboplatin/paclitaxel
RR 71.2% vs 47.3%
mPFS 9.5 vs 6.3 m WJTOG 3405 Gefitinib vs
cisplatin/docetaxel
RR 62.1% vs 32.2%
mPFS 9.2 vs 6.3 m NEJGSG002 Gefitinib vs
carboplatin/paclitaxel
RR 73.7% vs 30.7%
mPFS 10.8 vs 5.4 m EURTAC Erlotinib vs
cisplatin/docetaxel
RR 58.1% vs 14.9%
mPFS 9.7 vs 5.2 m OPTIMAL Erlotinib vs
gemcitabine/carboplatin
RR 83% vs 36%
mPFS 13.1 vs 4.6 m LUX-Lung 3 Afatinib vs
cisplatin/pemetrexed
RR 56% vs 23%
mPFS 11.1 vs 6.9 m LUX-Lung 6 Afatinib vs
gemcitabine/cisplatin
RR 66.9% vs 23%
mPFS 11.0 vs 5.6 m
• ROS1
Shaw AT, NEJM. 2014
Mok T, NEJM 2009
Mitsudomi T, Lancet Oncol 2010 Maemondo M, NEJM 2010 Zhou C, Lancet Oncol 2011
Rosell R, Lancet Oncol 2012 Sequist LV, J Clin Oncol 2013
Wu YL, Lancet Oncol 2014 Solomon BJ, NEJM 2014
Peters S, NEJM 2017
Pathology report – essential elements
• Morphology
• Essential IHC
• Molecular analysis
• PD-L1
LG AIOM 2016
Pathology report – sample management
LG AIOM 2016
Novello S, Ann Oncol 2016
0
PD-L1
Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252-64.
PD-L1
NIVOLUMAB PEMBROLIZUMAB ATEZOLIZUMAB
FDA NSCLC >1 pt-based ct NSCLC PD-L1≥50%
NSCLC PD-L1≥1%, >1 pt-based ct
NSCLC >1 pt-based ct
EMA NSCLC >1 pt-based ct NSCLC PD-L1≥50%
NSCLC PD-L1≥1%, >1 pt-based ct
AIFA NSCLC >1 pt-based ct NSCLC PD-L1≥50%
NSCLC PD-L1≥1%, >1 pt-based ct
PD-L1
Chae YW, Cl Lung Cancer 2016
PD-L1
• Intratumoral heterogeneity
• Dynamic evolution of immune response
• Biopsy site (lymph node vs parenchyma)
• Biopsy timing (archival vs new)
• Cytology vs histology
• Different assays
• Different cut-offs and scoring
• Pathologist expertise
clone Companion drug cutoff 22C3 (Dako) pembrolizumab 1%, 50%
28-8 (Dako) nivolumab 1%, 5%, 10%
SP142 (Ventana) atezolizumab 1%, 5%, 10%, 50%
(IC/TC)
SP263 (Ventana) durvalumab 25%
Herbst RS, Lancet 2016
Hirsch F, JTO 2017
PD-L1 testing
Rimm DL, JAMA Oncol 2017 Ratcliffe MJ, Clin Cancer Res 2017
PD-L1 testing
ICC for Pathologist Scores TC 0.86
IC 0.19
A.Z. – Pathology report
• Lung adenocarcinoma
• TTF1 +, p40 –
• EGFR WT exons 18-21
• ALK IHC neg (D5F3 clone)
• ROS1 not rearranged (FISH)
• PD-L1 42% (Dako 22C3 clone)
A.Z. – Pathology report
• Lung adenocarcinoma
• TTF1 +, p40 –
• EGFR WT exons 18-21
• ALK IHC neg (D5F3 clone)
• ROS1 not rearranged (FISH)
• PD-L1 42% (Dako 22C3 clone)
Rimm DL, JAMA Oncol 2017
1st L Immuno 1st L Chemo