News of the year: impact on clinical practice Istituto Toscano Tumori

Presentazione sul tema: "News of the year: impact on clinical practice Istituto Toscano Tumori"— Transcript della presentazione:

1 News of the year: impact on clinical practice Istituto Toscano Tumori
Federico Cappuzzo Istituto Toscano Tumori Ospedale Civile Livorno-Italy Slide di presentazione modificata per stile Istituto Toscano Tumori –Livorno, Italy

2 LACE Meta-analysis: Survival Curves
Titolo : Modificato da calibri 25 a calibri 30 Istituto Toscano Tumori –Livorno, Italy

3 Massuti B, et al. ASCO 2015 Istituto Toscano Tumori –Livorno, Italy
Randomized phase III trial of customized adjuvant chemotherapy (CT) according BRCA-1 expression levels in patients with node positive resected Non-Small Cell Lung Cancer (NSCLC)<br /> SCAT :A Spanish Lung Cancer Group trial <br /> Massuti B, et al. ASCO 2015 Istituto Toscano Tumori –Livorno, Italy

4 Massuti B, et al. ASCO 2015 Istituto Toscano Tumori –Livorno, Italy
Slide 5 Massuti B, et al. ASCO 2015 Istituto Toscano Tumori –Livorno, Italy

5 Customized BRCA1 Adjuvant Treatment in Stage II-II NSCLC (SCAT)
Massuti B, et al. ASCO 2015 Istituto Toscano Tumori –Livorno, Italy

6 Results/1 (cut-off March 15th 2015): Overall survival
Massuti B, et al. ASCO 2015 Istituto Toscano Tumori –Livorno, Italy

7 ITACA Adjuvant Trial Pharmacogenomic
Taxanes High Profile 4 Control TS Pem High Profile 3 Low Control Cis/Gem ERCC1 High Profile 2 Low Control TS Cis/Pem Low Profile 1 Control Control = Investigators’ choice; Primary end-point =overall survival; Sample size =700 patients Istituto Toscano Tumori –Livorno, Italy

8 Phase III trial of carbo-paclitaxel +/- bevacizumab in metastatic NSCLC: OS
12 mo. 24 mo. 1.0 0.8 0.6 0.4 0.2 bevacizumab + CP CP 52% % 44% % HR: 0.77 (0.65, 0.93) Probability p= 0.007 Medians: 10.2, 12.5 Months Sandler A, NEJM 2006 Istituto Toscano Tumori –Livorno, Italy

9 Overall Survival Disease Free Survival
Randomized phase III trial of adjuvant chemotherapy with or without bevacizumab in resected non-small cell lung cancer (NSCLC): Results of E1505 Overall Survival Disease Free Survival OS hazard ratio (B:A): 0.99 95% CI: ( ) p=0.93 DFS hazard ratio (B:A): 0.98 95% CI: ( ) p=0.75 . Wakelee H, et al WCLC 2015 Istituto Toscano Tumori – Livorno, Italy

10 RADIANT trial design Tumor samples EGFR IHC+ and/or EGFR FISH+ (n=623)
Erlotinib 150mg/day No adjuvant chemotherapy Stage IB–IIIA NSCLC Complete surgical resection (N=973) Randomization stratified by: histology, stage, prior adjuvant chemo, EGFR FISH status, smoking status, country 90 d 2:1 2-yr treatment period Up to 4 cycles of platinum-based doublet (n=350) Placebo 180 d Radiology assessment: every 3 months on treatment and yearly during long-term follow up Primary endpoint: DFS Secondary endpoints: Overall survival (OS); DFS and OS in patients with del19/L858R (EGFR M+) Kelly K, JCO 2015 Istituto Toscano Tumori – Livorno, Italy

11 RADIANT: DFS and OS in the whole study population
Placebo Erlotinib Erlotinib Placebo Kelly K, JCO 2015 Istituto Toscano Tumori – Livorno, Italy

12 RADIANT: DFS and OS in EGFR mut+
Placebo Erlotinib Erlotinib Placebo Stage Ib-IIa: 59.8% versus 39% in erlotinib arm versus placebo arm Kelly K, JCO 2015 Istituto Toscano Tumori – Livorno, Italy

13 Take home message degli studi di terapia adiuvante
La chemioterapia basata sul platino rimane lo standard terapeutico adiuvante nei pazienti con carcinoma polmonare resecato La farmacogenomica non aiuta ad ottimizzare I risultati della terapia adiuvante (in attesa dello studio ITACA) L’aggiunta del bevacizumab alla chemioterapia adiuvante non migliora la sopravvivenza dei pazienti Nessun farmaco biologico è attualmente indicato come terapia precauzionale neppure in pazienti selezionati (esempio EGFR-TKIs nei pazienti con mutazione di EGFR) Istituto Toscano Tumori –Livorno, Italy

14 Locally advanced (stage III) NSCLC: a heterogeneous group
“surgical multimodality” “non-surgical multimodality” unresectable some IIIA-N2 some T4-N0/1 bulky IIIA-N2 most IIIB Induction chemo  surgery Induction CTRT potentially resectable Radiotherapy Systemic therapy Vansteenkiste ERS 2008 Istituto Toscano Tumori –Livorno, Italy

15 Concurrent versus sequential chemoradiation: metaanalysis of survival
Auperin et al J Clin Oncol 2010; 28:2181 Istituto Toscano Tumori –Livorno, Italy

16 Senan S, et al. ASCO 2015 Istituto Toscano Tumori –Livorno, Italy
Final overall survival results of the phase III PROCLAIM trial: Pemetrexed, cisplatin or etoposide, cisplatin plus thoracic radiation therapy followed by consolidation cytotoxic chemotherapy in locally advanced nonsquamous non-small cell lung cancer Senan S, et al. ASCO 2015 Istituto Toscano Tumori –Livorno, Italy

17 PROCLAIM: Study Design
Senan S, et al. ASCO 2015 Istituto Toscano Tumori –Livorno, Italy

18 Senan S, et al. ASCO 2015 Istituto Toscano Tumori –Livorno, Italy
Slide 11 Senan S, et al. ASCO 2015 Istituto Toscano Tumori –Livorno, Italy

19 Senan S, et al. ASCO 2015 Istituto Toscano Tumori –Livorno, Italy
Slide 17 Senan S, et al. ASCO 2015 Istituto Toscano Tumori –Livorno, Italy

20 OS with CDDP-VP16 versus CBDCA-Paclitaxel concomitant with RT
Santana-Davila et al. JCO 2014 Istituto Toscano Tumori –Livorno, Italy

21 Take home message degli studi sul trattamento della malattia localmente avanzata
La chemioradioterapia concomitante è lo standard terapeutico per la malattia localmente avanzata non resecabile La chemioterapia con platino-Vepesid rimane una valida opzione in concomitanza con la radioterapia La tossicità può essere ridotta utilizzando platino- pemetrexed ma Solo nei non squamosi Con aumento dei costi Carbo-taxolo valida alternativa low-cost Istituto Toscano Tumori –Livorno, Italy

22 Istituto Toscano Tumori – Livorno, Italy
Pembrolizumab (MK-3475) in Patients With Extensive-Stage Small Cell Lung Cancer: Preliminary Safety and Efficacy <br />Results from KEYNOTE-028 Istituto Toscano Tumori – Livorno, Italy

23 Ott P, et al. ASCO 2015 Istituto Toscano Tumori – Livorno, Italy
Change From Baseline in Tumor Size <br />(RECIST v1.1, Investigator Review) Ott P, et al. ASCO 2015 Istituto Toscano Tumori – Livorno, Italy

24 Presented By Scott Antonia at 2015 ASCO Annual Meeting
Phase I/II Study (CheckMate 032) of Nivolumab<br />With or Without Ipilimumab for Treatment of Recurrent Small Cell Lung Cancer (SCLC) Presented By Scott Antonia at 2015 ASCO Annual Meeting

25 CheckMate 032 Study Design
Scott A, et al. ASCO 2015 Istituto Toscano Tumori – Livorno, Italy

26 Summary of Clinical Activity
Scott A, et al. ASCO 2015 Istituto Toscano Tumori – Livorno, Italy

27 Tumor Responses (PD-L1 expression)
Scott A, et al. ASCO 2015 Istituto Toscano Tumori – Livorno, Italy

28 Scott A, et al. ASCO 2015 Istituto Toscano Tumori – Livorno, Italy
Overall Survival Scott A, et al. ASCO 2015 Istituto Toscano Tumori – Livorno, Italy

29 Phase I Study of a delta-like protein 3 (DLL3)-Targeted Antibody Drug Conjugate Rovalpituzumab in SCLC DLL3, is a protein encoded by the DLL3 gene This gene encodes a member of the delta protein ligand family. This family functions as Notch ligands DLL3 is higly expressed in 70% of SCLC Rova-T is an antibody drug conjugate (ADC) consisting of : An antibody A linker A chemotherapy

30 Rova-T: Best Response Data in Evaluable SCLC Patients 0
Rova-T: Best Response Data in Evaluable SCLC Patients 0.2 mg/kg q3w and 0.3 mg/kg q6w cohorts (n=53) Expression H-Score SCLC % High 180+ 70% Intermediate 90-180 11% Low 0-90 19% Unknown NA DLL3 tested in 48 cases, with 33 cases with high levels of expression with 34% RR and 31% SD All patients received the drug as second or third-line Pietanza C, et al. ECC 2015 Istituto Toscano Tumori – Livorno, Italy

31 Take home message sul microcitoma polmonare
L’immunoterapia rappresenta una potenziale nuova opzione terapeutica per il microcitoma polmonare con promettenti dati preliminari In monoterapia In combinazione con altri immunoterapici Rovalpituzumab ha mostrato di indurre remissione di malattia in pazienti pretrattati e selezionati per espressione di DLL3 Istituto Toscano Tumori –Livorno, Italy

32 IFCT MAPS: study design
Scherpereel, et al. WCLC 2015 Istituto Toscano Tumori –Livorno, Italy

33 IFCT MAPS: OS 1.0 0.8 0.6 0.4 0.2 OS estimate 10 30 40 50 20 60 HR 0.76 (0.61–0.94) p=0.0127 Pemetrexed + cisplatin (n=225) 225 7 No. at risk 223 166 171 77 91 36 45 8 16 Time (months) 18.82 16.07 Pemetrexed + cisplatin + bevacizumab (n=223) Scherpereel, et al. WCLC 2015 Istituto Toscano Tumori –Livorno, Italy

34 IFCT MAPS: OS by subgroup
All (n=448) Male (n=338) Female (n=110) Age <65.7 years (n=224) Age ≥65.7 years (n=224) PS 0/1 (n=433) PS 2 (n=15) Epithelioid (n=361) Sarcomatoid (n=42) Mixed (n=45) Smokers (n=254) Never smokers (n=194) Platelet <400x109/L (n=336) Platelet ≥400x109/L (n=111) Haemoglobin ≤14g/L (n=309) Haemoglobin >14g/L (n=139) Leucocytes ≥8.3x109/L (n=191) Leucocytes <8.3x109/L (n=256) EORTC good prognosis (n=320) EORTC poor prognosis (n=128) 0.5 1.0 1.5 2 Favours triplet Scherpereel, et al. WCLC 2015 Favours doublet Istituto Toscano Tumori –Livorno, Italy

35 Take home message sul mesotelioma
L’aggiunta di bevacizumab all’attuale standard terapeutico di platino-pemetrexed aumenta la sopravvivenza dei pazienti con mesotelioma pleurico La riduzione del rischio di morte è rilevante (24%) Il vantaggio in sopravvivenza è presente in tutti i sottogruppi Nuovo standard terapeutico se bevacizumab verrà registrato con questa indicazione Istituto Toscano Tumori –Livorno, Italy