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 ilaria.attili@iov.veneto.it

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

Optimization of sample management is essential for adequate diagnosis of NSCLC

At least EGFR and ALK should be tested in all new diagnosis of lung

adenocarcinoma. If possible, multipanel molecular testing could be useful to guide

treatment in further lines

PD-L1 testing is controversial but essential in guiding treatment choice from the

first line in NSCLC

Different PD-L1 assays are equally approved but attention should be payed when

interpreting the results because it can change treatment approach

Conclusions