COOL - Community in Oncology On Lung Cancer www.esanum.it/cool

1. Caso clinico prima linea
• Donna, 50 anni ricoverata in U.O. Pneumologia
• Fumatrice (20 sig/die da 30 anni)
• PS: 1
• Sintomi: tosse e dispnea da sforzo
• Comorbidità: ipertensione ben controllata

2. Caso clinico prima linea
• RX torace: lesioni nodulari bilaterali
• EO: linfonodo sopraclaveare destro di circa 2.0 cm
• TC Total-Body con mdc: tumefazione linfonodale sopraclaveare
destra 1.7 cm. Multiple lesioni eteroplasiche polmonari periferiche
bilaterali, di cui la maggiore di 3 cm al lobo inferiore di destra,
linfoadenopatie mediastiniche e retrocarenali (max 3 cm)
• PET total body: iperaccumulo a livello della regione sopraclaveare
destra (SUV 8.9), delle multiple lesioni polmonari bilaterali (SUV
max 12.5), e a livello madiastinico (SUV 10.7)
cT4 N3 M1a – STADIO IV

3. Caso clinico prima linea
• Broncoscopia con brushing e BAL: non
alterazioni della canalizzazione bilateralmente
fino al limite della visione endoscopica, in
rapporto all’ubicazione periferica delle lesioni.
Brushing: negativo
BAL: positivo per carcinoma NOS

4. Per decidere un trattamento di prima linea
più appropriato è mandatorio determinare
l’istotipo e lo stato mutazionale di EGFR.
E’ necessario:
• asportare il linfonodo sopraclaveare destro
oppure
• effettuare un ago aspirato dello stesso
oppure
• ripetere la broncoscopia con il tentativo
di un agobiopsia transbronchiale?
Caso clinico prima linea: Quesito 1

5. Caso clinico prima linea:
Risposta Quesito 1
• Asportazione linfonodo sopraclaveare destro:
adenocarcinoma con EGFR non mutato

6. non-squamousnon-squamous squamoussquamous
?????? ?????? ??????
NSCLCNSCLC
considerconsider
gefitinibgefitinib
EGFR mut+EGFR mut+
First-line approach in advanced NSCLC
EGFR wt or unknownEGFR wt or unknown

7. EGFR-TKIs and EGFR Mutations First-Line
Randomized Phase III Studies
Study Entry Criteria and
Therapy (no.pts)
HR for PFS
(EGFR mut +)
HR for OS
(EGFR mut +)
IPASS
Mok
NEJM 2009
Asiatic, never- & light –
smokers, adenocarcinoma
(EGFR mut + 59.7%)
GEF (609) vs. CBDCA+PAC
(608)
0.48
(0.36-0.66)
0.91 *
(0.76-1.10)
*overall population
First – SIGNAL
Proc. IASLC
2009
Adenocarcinoma, Never-
smokers
(EGFR mut + 44%)
GEF (159) vs. CDDP+GEM
(150)
0.61
(0.30-1.22)
0.82
(0.35-1.92)
NEJ002
Maemondo
NEJM 2010
EGFR Mutation + (all)
GEF (98) vs. CBDCA+PAC
(96)
0.30
(0.22-0.41)
GEF 30.5 mos
CT 23.6 mos
P = 0.31
WJTOG3405
Mitsudomi
Lancet Oncol 2010
EGFR Mutation + (all)
GEF (86) vs. CDDP+DOC
(86)
0.49
(0.34-0.71)
NA
EURTAC (EU) EGFR Mutation + (all)
ERL vs. Platinum-based
chemo
? ongoing ? ongoing

8. Quale terapia di prima linea?
• Cisplatino + Pemetrexed
• Carboplatino + Paclitaxel + Bevacizumab
• Cisplatino + Gemcitabina + Bevacizumab
Caso clinico prima linea: Quesito 2

9. non-squamousnon-squamous squamoussquamous
JMDBJMDB
HR 0.81HR 0.81
subset beva-eligiblesubset beva-eligible
ECOG HR 0.80ECOG HR 0.80
AVAiL HR 0.98AVAiL HR 0.98
cisplatin-cisplatin-
pemetrexedpemetrexed
doublet +doublet +
bevacizumabbevacizumab
platinumplatinum
doubletdoublet
NSCLCNSCLC
considerconsider
gefitinibgefitinib
EGFR mut+EGFR mut+
*Beva-eligible:*Beva-eligible: non-squamous, no grnon-squamous, no gr ≥≥2 haemoptysis, no invasion of major vessels,2 haemoptysis, no invasion of major vessels,
no cavitation, no uncontrolled hypertension, no recent history of thrombosis,no cavitation, no uncontrolled hypertension, no recent history of thrombosis,
no hemorrhagic disorders, no recent anticoagulationno hemorrhagic disorders, no recent anticoagulation
First-line approach in advanced NSCLC
EGFR wt or unknownEGFR wt or unknown

10. JMDB (ADK)* E4599 (ADK)° AVAiL (NSQ)^
(CDDP+PEM) (CBDCA+PAC+BEV) (CDDP+GEM+BEV)
OR (%)
PFS (mos)
OS (mos)
Female OS (NSQ mos)
G3/4 Toxicity (%) (NSQ)
Neutropenia
FN
PLT
Hypertension
Any G Alopecia
Outcomes in Adenocarcinoma histology
31.9 35 34.6-37.8
5.5 6.6 6.5-6.7
12.6 14.2 13.4-13.6
13.8 13.3 NR
15.1 25.5 36-40
1.3 5.2 2.0
4.1 1.6 23-27
NR 7.0 6-9
11.9 NR NR52% (Scagliotti JCO 2002) 10%
*Scagliotti JCO 2008; Scagliotti Oncologist 2009
°Sandler NEJM 2006; Sandler JTO 2010
^Reck JCO 2009; Reck Ann Oncol 2010

11. S130: Pem/CarboS130: Pem/Carbo  PemPem vs.vs. Pac/Carbo + BevPac/Carbo + Bev  BevBev
Arm B:
360
Randomized
Patients
Stratification
factors:
•Disease stage
• Performance
status
•Gender
R
A
N
D
O
M
I
Z
E
Pemetrexed 500 mg/m2
Carboplatin AUC 6
q 21 days X 4 cycles*
Paclitaxel 200 mg/m2
Carboplatin AUC 6
Bevacizumab 15 mg/kg
q 21 days X 4 cycles*
Arm A:
Pemetrexed 500 mg/m2
q 21 days until PD or
treatment discontinuation
Bevacizumab 15 mg/kg
q 21 days until PD or
treatment discontinuation
*In both treatment arms, patients with CR, PR, or SD after 4 cycles of
induction therapy continue on to maintenance therapy.
Induction Therapy Maintenance Therapy
Zinner R, Saxman S, Peng G, et al. Randomized, Open-Label Study of Pemetrexed/Carboplatin Followed by Maintenance
Pemetrexed Versus Paclitaxel/Carboplatin/Bevacizumab Followed by Maintenance Bevacizumab in Patients With Advanced Non-
Small Cell Lung Cancer (NSCLC) of Nonsquamous Histology. ASCO - Chicago, IL, Jun 4-8, 2010 – JCO 28, abstr. TPS290.
Primary endpoint:
PFS without G4
toxicity,
HR=0.75, N=360