1. Case 1 Male, 55 years ECOG PS0 No comorbidities
Former smoker (1 pack/day for 20 years)
Surgery (2010): Lung adenocarcinoma
Stage IIIA (pT2, pN2, M0)
Adjuvant treatments: Cisplatinum- Vinorelbine x 4cycles
followed by RT (50 Gy)
Si parl

2. Adenocarcinoma: EGFR/EML-ALK: WT
CT scan (September 2013)
Si parl
Adenocarcinoma: EGFR/EML-ALK: WT
First-line treatment: Carboplatinum- Pemetrexed x 6cycles

3. CT scan evaluation (September 2014)
Si parl
ECOG PS0
Symptoms: (Dyspnea G1)

4. Second-line treatment options (October 2014)
Docetaxel 75 mg/mq q21
(Shepherd et al, JCO 2000)
Tarceva 150 mg os/die
(Zhu et al, JCO 2008)
Si parl
Clinical Trial
Second-line treatment: Anti-PDL1 MoAb

5. CT scan evaluation after 4 cycles
Basal CT-scan (September 2014 )
CT-scan (December 2014 )
Si parl
Symptoms: DyspneaG1
Toxicities: astheniaG2, dizznessG1, artrhalgiaG1, rashG1, hipothyroidism

6. CT scan evaluation after 13 cycles
CT-scan (December 2014 )
CT-scan (July 2015 )
Si parl
Symptoms: DyspneaG1
Toxicities: astheniaG1, hipothyroidism hormone replacement

7. Treatment beyond RECIST 1.1 PD
Allowed by protocol if patients meet the following criteria:
Investigator-assessed clinical benefit
No rapid disease progression
Tolerance of study drug
Stable Performance Status
Don’t delay intervention to prevent serious complications of disease progression (CNS)
Subject signed informed consent, using an ICF describing any reasonably foreseable risk, or other alternative treatment options
Si parl

8. CT scan evaluation after 21 cycles
CT-scan (July 2015 )
CT-scan (January 2016 )
Si parl
Symptoms: DyspneaG2, CoughG1
Toxicities: astheniaG1, hipothyroidism hormone replacement

9. Anti- PDL1 Therapy: Efficacy/Tolerability
Anti-PDL1 MoAb
October 2014
January 2016 SD SD
SD (i-R) PD
N. cycles 4 8 13 21
Symptoms: dyspnea, cough G1 G2
Toxicities: asthenia, dizzness, artrhalgia, rash, hipothyroidism
G1-2
G0-1

10. Ir-Toxicities: Time of onset
Si parl
The majority of ir-AEs within first 3 months of therapy
Reckamp K, WCLC 2015

11. Second/Third-line treatment options (Europe, 2016)
Docetaxel 75 mg/mq q21
Tarceva 150 mg os/die
Nintedanib 200 mg os/bid +
Nivolumab 3 mg/kg q14
Ramucirumab + Docetaxel
Pembrolizumab
Si parl

12. Second/Third-line treatment options (January 2016)
Rebiopsy
Adenocarcinoma, EGFR, EML-ALK, ROS1: WT
Anti-PD1 MoAb: Nivolumab
(Already administered)
Si parl
Nintedanib 200 mg os/bid +Docetaxel 75 mg/mq q21
(EAP)

13. CT scan evaluation after 2 cycles
CT-scan (January 2016 )
CT-scan (April 2016 )
Si parl
Symptoms: DyspneaG1
Toxicities: astheniaG2, diarrheaG2, neutropeniaG2

14. Nintedanib + Docetaxel: Efficacy/Tolerability
Nintedanib 200 mg BID +
Docetaxel 75 mg/mq
Nintedanib 200 mg BID +
Docetaxel 60 mg/mq PR ?
N. cycles 2 5
Symptoms: Dyspnea, Cough G2 G1
Treatment Ongoing
Toxicities: Asthenia, Diarrhea G2 G1

15. Open questions???
- Which is the best second-line option/treatment sequence
in EGFR/ALK/ROS1 WT adenocarcinoma?
Are there any potential predictive biomarkers (clinical vs
radiological vs molecular)?
PD to immunotherapy (Clinical vs Radiological? i-RECIST?)
(Pseudo-PD vs Real-PD?)
- Long-term treatments: number of cycles? Costs?
Si parl
OS: more than 30 months…!!!

16. Case (AIOM) Male, 55 years ECOG PS0
Former smoker (1 pack/day for 20 years)
No comorbidities
Surgery (2010): Lung adenocarcinoma (pT2, pN2, M0)
Adjuvant treatments: Cisplatinum - Vinorelbine x 4cycles
followed by RT (50 Gy)
PET (September 2013): Recurrence disease (EGFR/ALK WT)
First-line treatment: Carboplatinum - Pemetrexed x 6cycles
Si parl