Second-line treatment for advanced NSCLC

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY Second-line treatment for advanced NSCLC Silvia Novello silvia.novello@unito.it

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY Life was so simple back in 2008

Di Maio M, EJC 2010

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY In 2017, second line therapy is no longer as simple We must now take into consideration: 1.Tumor histology 2.Molecular phenotype (EGFR, ALK, ROS1, etc), Cappuzzo 3.Frontline chemo components (i.e. bevacizumab) 4.Maintenance therapy (continuation, switch) 5. IO in First Line 6.Others (adequacy of tumor tissue, third party reimbursement, guidelines, pathways, etc)

INDUCTION MAINTENANCE 2 nd LINE 3 rd LINE

Di Maio M, JCO 2009

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY Clinical Lung Cancer 2014

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY Second line therapy Outside Clinical Trials (N=464, 86% of pts progressing after first line) Gridelli C et al, J Cancer Res Clin Oncol. 2014 De Marinis F et al, Clinical Lung Cancer 2014

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY Guidelines [ESMO-AIOM]

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY Cumulative probability Treatment Options Post-platinum Progression: Docetaxel Docetaxel was the first treatment to be approved for NSCLC patients with disease progression following first-line chemotherapy 1 1.0 Patients receiving docetaxel 75 mg/m 2 had OS of 7.5 months, compared with 4.6 months for those receiving BSC 2 Docetaxel-treated patients had a significantly higher 1-year survival rate compared with patients receiving vinorelbine or ifosfamide (32% vs. 19%; p=.025) 3 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 Docetaxel 75 mg/m 2 (n=55) BSC (n=49) 0.0 0 6 12 18 Survival (months) 1. Sanofi Aventis. Taxotere (docetaxel) prescribing information. Nov 2014 2. Shepherd FA et al. J Clin Oncol 2000;18:2095-103 3. Fossella FV et al. J Clin Oncol 2000;18:2354-62

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY Survival distribution function Treatment Options Post-platinum Progression: Pemetrexed in nonsquamous NSCLC Pemetrexed was approved for patients progressing after chemotherapy after it demonstrated non-inferiority vs. docetaxel, but with a better toxicity profile 1-3 In patients with nonsquamous histology, pemetrexed treatment resulted in a median OS of 9.3 months, compared with 8.0 months for docetaxel 4 Pemetrexed is only suitable for patients with nonsquamous histology 1 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 Pemetrexed Docetaxel Adjusted HR 0.78 (95% CI 0.61 1.00) 0 6 12 18 24 30 Survival (months) The increased use of pemetrexed in first-line treatment means docetaxel remains an option as subsequent therapy for patients of all histologies 1. Eli Lilly and Company. Alimta (pemetrexed) prescribing information. Sep 2013 2. Hanna N et al. J Clin Oncol 2004;22:1589-97 3. Weiss GJ et al. J Clin Oncol 2006;24:4405-11 4. Scagliotti G et al. Oncologist 2009;14:253-63

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY Overall survival (%) Treatment Options Post-platinum Progression: Erlotinib The EGFR TKI erlotinib is approved for use in unselected patients with disease progression after first-line chemotherapy 1 However, erlotinib was inferior to docetaxel for OS and PFS in patients without an EGFR mutation; other options may be preferred in this setting 2,3 Erlotinib is not recommended for patients with a poor classification following proteomic testing in patients with WT or unknown EGFR status 3,4 100 90 80 70 60 50 40 30 20 10 0 Cox model adjusted HR 0.73 (95% CI 0.53-1.00) Erlotinib Docetaxel 0 2 4 6 8 10 12 14 16 18 20 Survival (months) 1. Astellas Pharma and Genentech. Tarceva (erlotinib) prescribing information. June 2015 2. Garassino MC et al. Lancet Oncol 2013;14:981-8 3. NCCN Clinical Practice Guidelines for Non-Small Cell Lung Cancer, V.6.2015 4. Gregorc V et al. Lancet Oncol 2014;15:713-21

PROSE Patient Flow 285 patients randomized 263 included for primary analysis 3 major protocol violations 19 never received therapy Chemotherapy (129) Erlotinib (134) VS-G 88 (68%) VS-P 41 (32%) VS-G 96 (72%) VS-P 38 (28%) The patient population was 72% male, 63% adenocarcinoma, 14% never smokers, 52% ECOG PS 0, and 41% ECOG PS 1, and was well balanced between arms. Third-line treatment at progression: CT arm: 41% overall (48% VS-G and 27% VS-P) ERL arm: 52% overall (56% VS-G and 39% VS-P) *PCR amplification/sanger sequencing of common mutations 01.07 PROSE Secondary Endpoint Analysis Vanesa Gregorc, MD

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY SQUAMOUS and NON-SQUAMOUS Carcinoma: rooms for improvements

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY Gene Methylation Mutations Translocations HYPERPLASIA DYSPLASIA CARCINOMA Air Space Limitless potential for replication INVASIVE CARCINOMA Cellular proliferation through independent growth signaling Promotion of survival signals and evasion of apoptosis Bronchial Epithelium Vascular recruitment and endothelial cell growth Tissue invasion and metastasis Adapted from Weinberg RA. Sci Am. 1996;275:62-70.

1:1 - Stage IV NSCLC after one platinum- based chemo +/- maintenance - Prior Bev allowed - All histologies - PS 0 or 1 R A N D O M I Z E Ramucirumab 10 mg/kg + Docetaxel 75 mg/m 2 q3wks N=628 Placebo + Docetaxel 75 mg/m 2 q3wks N=625 Treatment until disease progression or unacceptable toxicity Stratification factors: ECOG PS 0 vs 1 Gender Prior maintenance East-Asia vs. ROW Primary endpoint: Overall Survival Secondary endpoints: PFS, ORR, safety, patient-reported outcomes

ITT population Overall Survival (%) 100 80 60 40 20 0 RAM+DOC PL+DOC Censored Median (95% CI) Censoring Rate RAM+DOC 10.5 (9.5-11.2) 31.8% PL+DOC 9.1 (8.4-10.0) 27.0% RAM+DOC vs PL+DOC: Stratified HR (95% CI) = 0.886 (0.75-0.98) Stratified log-rank P =.023 Number at risk RAM+DOC PL+DOC 0 3 6 9 12 15 18 21 24 27 30 33 628 625 527 501 415 386 329 306 231 197 Survival Time (months) 156 129 103 86 70 56 45 36 23 23 11 9 2 0 36 0 0

Progression-Free Survival (%) ITT population, Investigator Assessment 100 80 60 40 20 0 RAM+DOC PL+DOC Censored Median (95% CI) Censoring Rate RAM+DOC 4.5 (4.2-5.4) 11.1% PL+DOC 3.0 (2.8-3.9) 6.7% RAM+DOC vs PL+DOC: Stratified HR (95% CI) = 0.76 (0.68-0.86) Stratified log-rank P = 0.0001 Number at risk RAM+DOC PL+DOC 0 3 6 9 12 15 18 21 24 27 30 33 628 625 383 301 204 172 120 95 Survival Time (months) 59 37 38 17 11 9 7 4 3 3 3 2 0 0 0 0 36 0 0

Response a, n (%) Ramucirumab + Docetaxel (n=628) Placebo + Docetaxel (n=625) CR 3 (0.5) 2 (0.3) p value Ramucirumab improved ORR and DCR in nonsquamous and squamous histologies PR 141 (22.5) 83 (13.3) SD 258 (41.1) 244 (39.0) PD 128 (20.4) 206 (33.0) Unknown 98 (15.6) 90 (14.4) ORR (95% CI) 144 (22.9) (19.7-26.4) 85 (13.6) (11.0-16.5) <.001 DCR (95% CI) 402 (64.0) (60.1-67.8) 329 (52.6) (48.6-56.6) <.001

Mean ASBI Total Score Mean LCSS Total Score QoL was measured using LCSS and ASBI A similar increase in symptom burden was observed in both treatment arms 100 80 60 40 20 0 100 n = Ramucirumab Placebo * * * * * * * * * * * * * * * * * * * * * * * * 0 2 3 4 5 6 7 8 9 10 Sum 30-day vis follow-up 484 491 422 433 353 300 326 266 261 217 233 196 178 144 167 120 127 102 111 86 366 367 296 305 Addition of ramucirumab had no detrimental effect on QoL 80 60 40 20 * * * * * * * * * * * * * * * * * * * * * * * * 0 0 2 3 4 5 6 7 8 9 10 Sum 30-day vis follow-up n = 493 501 457 443 358 306 338 274 270 218 240 199 181 149 171 125 129 102 112 87 375 372 300 311 Cycle

REVEL: Patient Disposition Screened (N=1825) Randomized (ITT) Population N=1253 Excluded (n=572) Patients not receiving treatment (n=4) RAM+DOC (N=628) RAM+DOC (N=627) * wt 33% mutant 2.4% unknown 64% PL+DOC (N=625) PL+DOC (N=618) * wt 31.5% mutant 2.9% unknown 65% Patients not receiving treatment (n=4) Reasons for discontinuation (N=613) PD 341 Adverse event 94 Subject decision 90 Investigator decision 37 Death due to adverse events 30 Death from study disease 12 Other 9 On treatment at data cutoff N=11 Safety Population N=1245 Reasons for discontinuation (N=611) PD 429 Adverse event 55 Subject decision 53 Investigator decision 19 Death due to adverse events 31 Death from study disease 14 Other 10 On treatment at data cutoff N=10 *Three PL+DOC arm patients were inadvertently treated with RAM and are therefore considered part of the RAM+DOC arm for the safety analyses, but the PL+DOC arm for the ITT efficacy analysis.

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY Forest plot PFS

Pembrolizumab - OS by PD-L1 expression - Keynote001 <1% 1-49% 50% 14.9% second line pts SC10.04: Second-Line Therapy and Beyond in Squamous Cell NSCLC - Silvia Novello Garon E et al, NEJM 2015

Pembrolizumab OS&PFS by PD-L1 expression Keynote010 HR 0.53 HR 0.76 OS most impressive in 50%, but superior with Pembrolizumab in all groups PFS benefit was superior in 50%, but not significant for either Pembrolizumab dose in 1% SC10.04: Second-Line Therapy and Beyond in Squamous Cell NSCLC - Silvia Novello Herbst R et al, The Lancet 2016

Keynote 010: OS by by Subgroups Pembrolizumab R Herbst et al., Lancet 2016

Forest plot PFS

Primary analysis from OAK, a randomized Phase 3 study comparing atezolizumab with docetaxel in 2L/3L NSCLC Locally advanced or metastatic NSCLC 1 2 prior lines of chemotherapy, including 1 platinum based Tumor specimen available Any PD-L1 status N=1,225 enrolled Primary endpoints (first 850 enrolled patients): OS in the ITT population OS in patients with 1% PD-L1 expression Secondary endpoints: ORR, PFS, DoR, safety Stratification factors PD-L1 expression Histology Prior chemotherapy regimens R 1:1 Atezolizumab 1200 mg IV q3w No Cross-Over Docetaxel 75 mg/m 2 q3w PD or loss of clinical benefit PD One of the largest studies that tested the role of an anti PDL-1 Mab in the setting of 2/3L NSCLC F. Barlesi, et al. ESMO 2016. Abstract LBA44_PR

Primary analysis from OAK, a randomized Phase 3 study comparing atezolizumab with docetaxel in 2L/3L NSCLC Overall survival (%) Characteristics Atezolizuma b n = 425 Docetaxel n = 425 Median age, y 63 64 65 y 45% 49% Male 61% 61% Nonsquamous 74% 74% Squamous 26% 26% ECOG PS, 0/1 37%/64% 38%/62% No. of prior therapies, 1/2 History of tobacco use 75%/25% 75%/25% Never 20% 17% Current/previous Known EGFR status, % 14% / 66% 16% / 67% Mutant/WT 10% / 75% 10% / 73% 100 80 60 40 20 0 0 Median 9.6 mo (95% CI, 8.6, 11.2) 3 Overall survival, ITT (n = 850) Atezolizumab Docetaxel HR, 0.73 a (95% CI, 0.62, 0.87) P=0.0003 Minimum follow-up = 19 months 6 9 12 15 18 Months Median 13.8 mo (95% CI, 11.8, 15.7) 21 24 27 No. at risk Atezolizumab 42 40 38 36 34 32 30 27 26 24 23 22 21 20 19 18 17 16 15 14 11 74 54 41 28 15 4 1 5 7 2 3 2 6 5 9 0 8 4 3 8 5 8 8 5 3 7 1 6 Docetaxel 42 39 36 33 31 28 26 23 21 19 17 16 15 14 13 12 11 10 98 90 70 51 37 28 16 6 3 5 0 5 6 1 6 3 6 9 5 9 8 1 0 2 3 6 4 F. Barlesi, et al. ESMO 2016. Abstract LBA44_PR

Overall survival (%) Overall survival, PD-L1 expression OS, PD-L1 expression on 1% TC or IC TC1/2/3 or IC1/2/3; 55% of patients 100 80 60 40 20 Median 10.3 mo (95% CI, 8.8, 12.0) HR, 0.74 a (95% CI, 0.58, 0.93) P=0.0102 Minimum follow-up = 19 months OS, PD-L1 expression on 50% TC or 10% IC TC3 or IC3; 16% of patients Atezolizumab HR, 0.41 Docetaxel 100 b (95% CI, 0.27, 0.64) P<0.0001 c 80 Minimum follow-up = 19 months Median 15.7 mo (95% CI, 12.6, 18.0) 60 40 20 Median 8.9 mo (95% CI, 5.6, 11.6) Median 20.5 mo (95% CI, 17.5, NE) 0 0 3 6 9 12 15 18 Months 21 24 27 No. at risk Atezolizuma 24 23 21 20 19 19 17 16 15 14 13 13 13 12 11 11 11 10 98 88 71 47 37 28 19 10 3 No. 1 at risk b 1 0 5 7 9 0 6 3 0 5 9 3 1 4 9 5 1 4 Atezolizuma 72 69 65 63 61 59 58 55 51 50 49 47 46 46 44 43 43 42 39 34 28 19 16 11 8 6 2 Docetaxel 22 20 18 17 16 14 13 12 11 10 96 89 81 74 72 65 62 59 55 51 41 28 18 15 8 3 1 b 2 0 5 2 1 8 6 4 6 5 Docetaxel 65 59 57 51 45 40 36 32 32 28 25 24 20 15 14 14 14 13 11 11 9 7 4 3 2 a Stratified HR; b Unstratified HR; c P values for descriptive purpose only. TC, tumor cells; IC, tumor-infiltrating immune cells; OS, overall survival. Barlesi et al, Atezolizumab Phase III OAK Study. 0 0 3 6 9 12 15 18 Months 21 24 27 F. Barlesi, et al. ESMO 2016. Abstract LBA44_PR

SQUAMOUS Carcinoma: rooms for improvements

Previous ESMO Guidelines

PFS (%) Smoking status and response to immunotherapy in NSCLC In studies of nivolumab, a history of smoking in patients with NSCLC was associated with improved clinical response and PFS PFS by smoking exposure 100 5 pack-yrs smokers (mpfs 1.7 months) Variable Smoking exposure ORR, % (n/n) [95% CI] P-value 80 60 40 >5 pack-yrs smokers (mpfs 2.2 months) HR (95% CI) = 0.41 (0.22, 0.74), P = 0.003 5 pack-yrs >5 pack-yrs 0 (0/14) [0, 23] 30 (20/66) [20, 43] 0.018 20 5 pack-yrs smokers >5 pack-yrs smokers 0 0 6 12 18 24 30 Months Since Treatment Initiation 14 3 1 1 1 1 75 28 16 12 7 1 HR = hazard ratio; mpfs = median progression-free survival; ORR = objective response rate; PFS = progression-free survival. Hellmann MD, et al. Poster presented at ESMO 2014 (asbtr. 1229PD).

SC10.04: Second-Line Therapy and Beyond in Squamous Cell NSCLC - Silvia Novello Campbell JD et al, Nat Genet 2016

Randomize 1:1 CheckMate 017 (NCT01642004) - Study Design Stage IIIb/IV SQ NSCLC NIVO 3 mg/kg IV Q2W, until PD or unacceptable toxicity n = 135 Primary: OS Secondary: Endpoints Investigator-assessed ORR 1 prior platinum doublet-based chemotherapy ECOG PS 0 1 N = 272 DOC 75 mg/m 2 IV Q3W, until PD or unacceptable toxicity n = 137 Investigator-assessed PFS Correlation between PD-L1 expression and efficacy (ORR, OS, PFS), Quality of life (LCSS) DBL: December 15, 2014 At time of DBL, 199 deaths (of 272 randomized pts) were reported (86% of 231 deaths required for final analysis) The boundary for declaring superiority for OS at the pre-planned interim analysis was P <0.03 DBL, data base lock; ECOG PS = Eastern Cooperative Oncology Group performance status; IV = intravenous; LCSS = lung cancer symptom scale; PD = progressive disease; PD-L1 = programmed cell death ligand 1; SQ = squamous; Q2W = every 2 weeks; Q3W = every 3 weeks Brahamer J et al, NEJM 2015

Checkmate 017: Updated follow-up Reckamp K et al., WCLC 2015 ORAL 02.01

Checkmate 017: Updated follow-up Reckamp K et al., WCLC 2015 ORAL 02.01

OS and PFS Hazard Ratios by PD-L1 Status PD-L1 expression Patients, n NIVO DOC Unstratified HR(95% Cl) OS 1% 63 56 0.69 (0.45, 1.05) <1% 54 52 0.58 (0.37, 0.92) 5% 42 39 0.53 (0.31, 0.89) <5% 75 69 0.70 (0.47, 1.02) 10% 36 33 0.50 (0.28, 0.89) <10% 81 75 0.70 (0.48, 1.01) Not quantifiable at baseline 18 29 0.39 (0.19, 0.82) PFS 1% 63 56 0.67 (0.44, 1.01) <1% 54 52 0.66 (0.43, 1.00) 5% 42 39 0.54 (0.32, 0.90) <5% 75 69 0.75 (0.52, 1.08) 10% 36 33 0.58 (0.33, 1.02) <10% 81 75 0.70 (0.49, 0.99) Not quantifiable at baseline 18 29 0.45 (0.23, 0.89) Spigel DR et al, ASCO 2015 NIVO 0 1 2 DOC

Forest plot PFS

Is there a room for targeted therapies (WITHOUT target) in SQUAMOUS carcinoma SC10.04: Second-Line Therapy and Beyond in Squamous Cell NSCLC - Silvia Novello

Lux Lung 8: Study design Stratified by East Asian vs. Non-East Asian SCC of the lung (Stage IIIB/IV) 1 Progressed after 4 cycles of a first-line platinum doublet ECOG PS 0 1 Adequate organ function 1:1 Afatinib 40 mg QD Erlotinib 150 mg QD Primary Endpoint: PFS by Independent Review Key secondary Endpoint: Overall Survival Other secondary Endpoints: ORR, DCR, tumor shrinkage, PRO, safety Dose escalation to 50 mg and dose reduction to 30 or 20 mg permitted Dose reduction to 100 or 50 mg permitted Tumor assessment at baseline, Weeks 8, 12, 16; every 8 weeks thereafter. 1. American Joint Committee on Cancer staging manual 7th edition Soria JC et al, ASCO 2015

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY Events, % LUX LUNG 8: Safety Afatinib (n=392) Erlotinib (n=395) Any AE 99.5 97.5 Drug-related AEs 93.4 81.3 AEs leading to dose reduction 26.5 14.2 AEs leading to discontinuations 20.2 17.0 CTCAE grade 3 or higher 57.1 57.4 Serious AEs 44.1 44.1 Drug-related fatal AEs 1.5 Afatinib 1.3 Erlotinib (N=392) (N=395) AE category, % All Grade 3 Grade 4 All Grade 3 Grade 4 Total with related AEs 93 25 1 81 16 1 Diarrhea 70 10 1 33 2 <1 Rash/acne* 67 6 0 67 10 0 Stomatitis* 29 4 0 9 0 0 Fatigue* 15 2 0 12 2 0 Nausea 13 1 0 7 1 0 Decreased appetite 13 1 0 10 1 0 Paronychia* 11 1 0 4 <1 0 Dry skin 9 1 0 10 0 0 Pruritus 8 <1 0 12 0 0 Vomiting 8 1 0 3 1 0 Dehydration 4 1 1 1 1 0 Goss GD IASLC Geneva 2015; Soria JC et al, ASCO 2015

LUX LUNG 8: Efficacy OS Forest plot PFS PFS SC10.04: Second-Line Therapy and Beyond in Squamous Cell NSCLC - Silvia Novello Soria JC et al, Lancet Oncol 2015

For Patients and Caregivers -A 60-page booklet in English, designed as an information guide for patients with SqCLC -The most frequent key questions from a patient with SqCLC

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY ADENOCarcinoma ( non-squamous ): rooms for improvements

LUME-Lung 1 Study Design Stage IIIB/IV or recurrent NSCLC patients after 1 st line chemotherapy (all histologies) R A N D O M I Z E 1:1 Nintedanib 200mg BID p.o., D2 21, + Docetaxel 75mg/m 2 IV, D1, 21-day cycles (n=655) Placebo BID p.o., D2 21, + Docetaxel 75mg/m 2 IV, D1, 21-day cycles (n=659) PD PD N=1314 Number of docetaxel cycles not restricted Monotherapy allowed after 4 cycles of combination therapy Stratification: ECOG PS (0 vs 1) Prior bevacizumab (yes vs no) Histology (squamous vs nonsquamous) Brain metastases (yes vs no) Primary end point: PFS Next analysis step only allowed if PFS confirmed with all PFS events at time point of OS analysis RECK LBA8011, ASCO 2013

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY LUME1: PFS TOTAL population ADENOCARCINOMA SQUAMOUS CARCINOMA Reck M et al, Lancet Oncol 2014

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY LUME1: OS Adenocarcinoma <9mo ADENOCARCINOMA Total population Reck M et al, Lancet Oncol 2014

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY LUME1: Safety Reck M et al, Lancet Oncol 2014

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY Forest plot PFS

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY CheckMate 057: Non Squamous pts Stage IIIB/IV NON-SQUAMOUS NSCLC 1 prior platinum doublet ECOG PS 0 1 Pre-treatment (archival or recent) tumor samples required for PD-L1 analysis Prior maintenance therapy allowed Prior TKI therapy allowed for known ALK translocation or EGFR mutation N = 582 Randomize 1:1 Nivolumab 3 mg/kg IV Q2W until PD or unacceptable toxicity n = 292 Docetaxel 75 mg/m 2 IV Q3W until PD or unacceptable toxicity n = 290 Patients stratified by prior maintenance therapy and line of therapy (second- vs third-line) Primary Endpoint OS Additional Endpoints ORR b PFS b Safety Efficacy by tumor PD-L1 expression Quality of life (LCSS) NIVOLUMAB NON SQ CHECK-MATE 057 (1) OS RR(%) Median (mos) 1-yr (%) PRETREATED III/IV PS0-1 NIVO 292 PTS DOC 290 PTS 19 12 51 p= 0.0015 HR 0.73 12 9.4 39 Borghaei h et al, NEJM 2015 Sep 27

UNIVERSITY OF TORINO DEPARTMENT OF ONCOLOGY Take Home Messages Chemotherapy is still present in second line NSCLC advanced patients Antiangiogenic copound found a second youth in second line Immunotherapy plays a relevant role in this setting.at least until it will move to first line Today even more than yesterday is crucial to design a treatment algorithm for these patients not to waste therapeutic approaches