Silvia Novello
silvia.novello@unito.it
Controlli di Qualità Nazionali di AIOM e SIAPEC-IAP 2016 nel NSCLC
Implicazioni Cliniche
Il mio Obiettivo
Abbiamo esempi “validi” in altre
patologie oncologiche?
Long-term results of adjuvant imatinib mesylate in localized,
high-risk, primary (GIST):
ACOSOG Z9000 (Alliance) intergroup phase 2 trial
DeMatteo RP et al, Ann Surg. 2013 Sep; 258(3): 422–29
Chapman PB et al, NEJM 2011; 364: 2507-2516
Improved survival with vemurafenib in
melanoma with BRAF V600E mutation
Qual’e’ stato il PRIMO step
Cosa significa applicare la Biologia Molecolare
alla Clinica
Kris M et al, JAMA. 2014;311(19):1998-2006
……..e per il paziente?
Adjuvant (N=123) Metastatic (N=121) Sex
Male Female
56 (46) 67 (54)
78 (64) 43 (36) Age
Median Range
58 (21-90)
62 (27-82) Cancer Type
Lung&Head and neck GI & Hepatobiliar Brest
Other
29 (24) 47 (38) 24 (20) 23 (18)
42 (35) 39 (32) 8 (7) 32 (36) Clinical Trial Experience
Yes No
100 (81) 23 (19)
75 (62) 46 (38) Previous Genetic Testing
Yes No
119 (97) 4 (3)
110 (91) 11 (9)
Pharmacogenetics and Genomics 2014, Vol 24 No 7
Pharmacogenetics and Genomics 2014, Vol 24 No 7
• The vast majority were accepting of pharmacogenomic testing and were willing to accept and delays in treatment to avail of testing (turnaround time 16 days, range 0-90).
• Ninety-two percent of patients were agreeable to an additional blood draw to facilitate testing, whereas just over half (55%) were agreeable to biopsy.
• One-fifth of patients indicated that they did not fully understand genetic testing and were worried about its implications.
Di quali dati stiamo parlando
EGFR
Maemondo M,et al. 2010 NEJM
Rosell R, et al. 2010 Lancet Oncology
Sequist L, et al. 2013 JCO
Alk
Solomon B, et al. 2014 NEJM
Nokihara H, et al. 2016 ASCO meeting
Different way to approve
14/11/2012
E di che NUMERI
stiamo parlando
40.000
4400 EGFR
2000 Alk
Cosa dovremo presto aggiungere
KEYNOTE-024: Pembrolizumab vs platinum-based chemotherapy as first-line therapy for advanced NSCLC with a PD-L1 tumor proportion
score (TPS) ≥50%
M. Reck, et al. ESMO 2016. Abstract LBA8_PR Key endpoints Primary: PFS (RECIST v1.1 per blinded, independent central review)
Secondary: OS, ORR, safety
Exploratory: DOR Key eligibility criteria
• Untreated stage IV NSCLC
• PD-L1 TPS ≥50%
• ECOG PS 0-1
• No activating EGFR mutation or
ALK translocation
• No untreated brain metastases
• No active autoimmune disease requiring systemic therapy
Pembrolizum ab 200 mg IV
Q3W (2 years)
PD
a
Pembrolizu mab 200 mg
Q3W for 2 years
Platinum-doublet chemotherapy
(4–6 cycles)
1934 patients entered screening
1729 submitted samples for PD-L1 assessment
1653 samples evaluable for PD-L1
500 TPS ≥50%
(30%)
1153 TPS
<50%
R (1:1) N=305
Assessed per RECIST v1.1 by blinded, independent central review.
Data cut-off: May 9, 2016.
1.Reck et al NEJM 2016; DOI: 10.1056/NEJMoa1606774; Reck, et al. ESMO 2016. Abstract LBA8_PR.
No. at risk Pembro Chemo
154 104 89 44 22 3
151 99 70 18 9 1
1 0 Events,
n
Median, mo
HR
(95% CI) P Pembro 73 10.3 0.50
(0.37–0.68) <0.001 Chemo 116 6.0
62%
50%
0 3 6 9 12 15 18 21
0 10 20 30 40 50 60 70 80 90 100
Time (months) 48%
15%
PFS (%)
Progression-free survival
KEYNOTE-024: PFS
KEYNOTE-024: OS
Data cut-off: May 9, 2016M.
1.Reck et al NEJM 2016; DOI: 10.1056/NEJMoa1606774; Reck, et al. ESMO 2016. Abstract LBA8_PR.
No. at risk Pembro Chemo
154 136 121 82 39 11 0
151 123 106 64 34 7 0
2 1 Events,
n
Median, mo
HR
(95% CI) P Pembro 44 NR 0.60
(0.41–0.89) 0.005
Chemo 64 NR
80%
72%
0 3 6 9 12 15 18 21
0 10 20 30 40 50 60 70 80 90 100
Time (months) 70%
54%
Overall survival (%)
Overall survival
• DMC recommended the trial be stopped because of superior efficacy observed with pembrolizumab
• US FDA: approved for treatment-naive advanced NSCLC that highly expresses PD-L1
• EU EMA: submitted for approval for the same population
Dove non c’è ancora uno “standard”
Barlesi F et al, The Lancet Jan 2016
