Immunoterapia nel 2019 tra sogno e realtà
Vanna Chiarion Sileni IOV-IRCCS, Padova
vanna.chiarion@iov.veneto.it
Tumors with the higher frequency of responses to PD1-/PD-L1 Blockade
• Hodking’ Lymphoma (PD-L1,PD-L2 overexpression/gene amplification)
• Merkel cell carcinoma (MCPyV Ags, and UV mutations)
• Cancers with MSI (high TML)
• Desmoplastic Melanoma (UV mutations)
2018 Nobel Prize in Medicine report
Jul 2017 Apr 2019
Male 67 y-old, 2015 MCC ptXN1bM0, S+RT, Mar 2017 node mets
Anti PD-1: better activity and efficacy in untreated patients 5-y OS Pembrolizumab KEYNOTE-001
All pts
Untreated
O’Hamid et al Ann Oncol 1-7,2019 Hodi FS et al. Lancet Oncol 2018
4-y OS Nivolumab Checkmate 067
Keynote-006: KM Estimates of OS First-Line Treatment
C.Robert et alLancet Oncol. 2019 Sep;20(9):1239-51
45.7
MS 25.8 MS 23.8 MS 11.5 MS 12.6
Nivolumab in different subtypes in patient progressed after ipilimumab
P Nathan et al EJC 2019
No objective response to PD-1 Ab therapy was seen.
Best response to treatment was stable disease in four patients (15).
Anti-PD- 1antibodies in metastatic uveal melanoma: a treatment option?
Cancer Medicine 2017; 6(7):1581–1586
ORR: 4.7%
MS: Pembro 14 months Nivo 10
O.Hamid et al. BJC, 2019
O.Hamid et al. BJC, 2019
Male 62 y-old, gastric AC G2 cT3N3M1c, PD after 3 cycles CF
Sep 2016 Pem 200 mg q 21
Aug 2019 off therapy in PR from Apr 2018
DFS from discontinuation of pembrolizumab in patients who discontinued after CR (No 89)
24 month-DFS 85.8%
Survival in NIVO+IPI Patients Who Discontinued Treatment During Induction Due to an AE
PFS OS
Months
OS (%)
Patients at risk:
Did not discontinue treatment due to a treatment-related AE Discontinued treatment due to a treatment-related AE
0 69
73
74 66 54 53 51 48 47 47 46 44 43 42 41 37 35 21 2 0 143
166
187 130 122 118 111 107 107 101 97 95 94 89 86 84 82 51 7 0
10 20 30 40 50 60 70 80 90 100
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 Months
PFS (%)
Patients at risk:
Did not discontinue treatment due to a treatment-related AE Discontinued treatment due to a treatment-related AE
0 40
57
74 34 27 27 25 23 22 20 20 19 18 18 18 16 11 5 0 0 91
111
187 82 74 71 67 62 57 55 52 48 47 45 44 40 31 11 3 0
10 20 30 40 50 60 70 80 90 100
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 Discontinued treatment due to a
treatment-related AE during induction Did not discontinue treatment due to a treatment-related AE
Discontinued treatment due to a treatment-related AE during induction Did not discontinue treatment due to a treatment-related AE 35%
33%
35%
30%
59%
51%
54%
46%
Discontinued during
induction Did not discontinue Median, mo
(95% CI)
11.1 (6.9, 26.7)
8.6 (5.3, 13.2) HR (95% CI)
versus NIVO
0.83
(0.58, 1.17) −
Discontinued during induction
Did not discontinue due to a TRAE Median, mo
(95% CI)
NR (30.5, NR)
37.1 (25.1, NR) HR (95% CI)
versus NIVO
0.78
(0.53, 1.14) −
Hodi FS et al. Lancet Oncol 2018
ASCO 2016
Baseline LDH and OR
ASCO 2018
Progression-Free Survival – Asymptomatic Patients
Presented By Hussein Tawbi at 2019 ASCO Annual Meeting
ORR 55%
Baseline Jul 2013
Sep 2013
262 BMS 066 Male 67-y old, pT4bN3M1b NRAS mut (p.Q61L del)
Melanoma cuoio capelluto, BRAF wt, cKit wt, NRAS wt, pT4aN0M1b. Nov 2011, male, DOB:1936
Feb 2012
Aug 2012
Ipi 3 vs 10 BMS169
Mar 2012
Jun 2013
Ipi 3 vs 10 BMS169
Jan 2014
Nivo 3mg/kg Checkmate 037
Nov 2017
Mar 2018
Nivo FD+Relatlimab BMS224-020
The majority of patients with metastatic melanoma are not represented in pivotal phase III immunotherapy trials
EJC: 74, 89-95;2017
mOS= 5.43 mos mOS= 18.3 mos mOS= 7.9 mos The majority of patients with metastatic melanoma are
not represented in pivotal phase III immunotherapy trials
EJC: 74, 89-95;2017
