At the Frontline in ALK+ NSCLC: Practical Approaches to TKI Therapy
PeerVoice
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Jul 19, 2024
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About This Presentation
Raffaele Califano, MD discusses lung cancer in this CME activity titled "At the Frontline in ALK+ NSCLC: Practical Approaches to TKI Therapy." For the full presentation, please visit us at www.peervoice.com/WAD870.
Slide Content
PeerVoice
At the Frontline in ALK+ NSCLC: Practical Approaches to TKI Therapy
Learning Objectives
Describe the molecular aberrations and associated patient characteristics that
influence response to treatment modalities in ALK-positive non-small cell lung
cancer (NSCLC)
Apply evidence-based approaches to balance the benefits of efficacy with risks
of treatment-related toxicities in consolidated therapy combinations used in the
management of ALK+ NSCLC
Formulate evidence-based strategies to identify and manage common and
serious adverse events (AEs) associated with tyrosine kinase inhibitors (TKIs)
Apply evidence-based approaches to balance the benefit-risk ratio in the
selection of appropriate treatment modalities for patients with ALK+ NSCLC and
central nervous system (CNS) metastases
PeerVoice is an EBAC® accredited provider since 2022.
ice.com/WAD870
At the Frontline in ALK+ NSCLC: Practical Approaches to TKI Therapy
Learning Objectives
Describe the molecular aberrations and associated patient characteristics that
influence response to treatment modalities in ALK-positive non-small cell lung
cancer (NSCLC)
Apply evidence-based approaches to balance the benefits of efficacy with risks
of treatment-related toxicities in consolidated therapy combinations used in the
management of ALK+ NSCLC
Formulate evidence-based strategies to identify and manage common and
serious adverse events (AEs) associated with tyrosine kinase inhibitors (TKIs)
Apply evidence-based approaches to balance the benefit-risk ratio in the
selection of appropriate treatment modalities for patients with ALK+ NSCLC and
central nervous system (CNS) metastases
PeerVoice is an EBAC® accredited provider since 2022.
ice.com/WAD870
PeerVoice
Part 1 of 4: ALK+ NSCLC: The Molecular Aberrations Shaping
the Clinicopathological Picture
Raffaele Califano, MD
Honorary Professor
Division of Cancer Sciences, The University of Manchester
Consultant in Medical Oncology
The Christie NHS Foundation Trust
Manchester, United Kingdom
Copyright © 2010-2024, PeerVoice
Part 1 of 4: ALK+ NSCLC: The Molecular Aberrations Shaping
the Clinicopathological Picture
Raffaele Califano, MD
Honorary Professor
Division of Cancer Sciences, The University of Manchester
Consultant in Medical Oncology
The Christie NHS Foundation Trust
Manchester, United Kingdom
Copyright © 2010-2024, PeerVoice
PeerVoice
Disclosures
Raffaele Califano, MD, has a financial interest/relationship or affiliation in the form of:
Consultant for Amgen Inc.; AstraZeneca; Bayer AG; Bristol Myers Squibb Company; Eli
Lilly and Company; F. Hoffmann-La Roche Ltd, Janssen Inc.; Merck Sharp & Dohme
Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; Sanofi; and Takeda Pharmaceutical
Company Limited.
Stock Shareholder in Supportive Care.
Advisory Board for Amgen Inc.; AstraZeneca; Bayer AG; Bristol Myers Squibb
Company; Eli Lilly and Company; F. Hoffmann-La Roche Ltd.; Janssen Inc.; Merck
Sharp & Dohme Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; Sanofi; and Takeda
Pharmaceutical Company Limited.
Grants paid to institution for conduct of clinical trials or contracted research for
AbbVie Inc.; AstraZeneca; Eli Lilly and Company; F. Hoffmann-La Roche Ltd.; Janssen
Inc.; Merck Sharp & Dohme Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; and Takeda
Pharmaceutical Company Limited.
www.peervoice.com/WAD870 Copyright © 2010-2024, PeerVoice
Disclosures
Raffaele Califano, MD, has a financial interest/relationship or affiliation in the form of:
Consultant for Amgen Inc.; AstraZeneca; Bayer AG; Bristol Myers Squibb Company; Eli
Lilly and Company; F. Hoffmann-La Roche Ltd, Janssen Inc.; Merck Sharp & Dohme
Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; Sanofi; and Takeda Pharmaceutical
Company Limited.
Stock Shareholder in Supportive Care.
Advisory Board for Amgen Inc.; AstraZeneca; Bayer AG; Bristol Myers Squibb
Company; Eli Lilly and Company; F. Hoffmann-La Roche Ltd.; Janssen Inc.; Merck
Sharp & Dohme Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; Sanofi; and Takeda
Pharmaceutical Company Limited.
Grants paid to institution for conduct of clinical trials or contracted research for
AbbVie Inc.; AstraZeneca; Eli Lilly and Company; F. Hoffmann-La Roche Ltd.; Janssen
Inc.; Merck Sharp & Dohme Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; and Takeda
Pharmaceutical Company Limited.
www.peervoice.com/WAD870 Copyright © 2010-2024, PeerVoice
PeerVoice
ALK Gene Rearrangement in NSCLC
EML4-ALK Variants in NSCLC
EML4-ALK
16420
£6420
£20;A20
£14,420
EI8;A20
EISA20
£2;A20
ETA20
TFG-ALK
KIFS-AUX
Mooiea-con Ml tyrosine kinase
domain domain
www.peervoice.com/WAD870
FISH
IHC
NGS
Detection Methods
Time consuming
Expensive
Requires expertise
Widely available
Recommended by
international guidelines
Tumour or plasma
samples can be used
Multiplex reflex testing
Copyright © 2010-2024, PeerVoice
ALK Gene Rearrangement in NSCLC
EML4-ALK Variants in NSCLC
EML4-ALK
16420
£6420
£20;A20
£14,420
EI8;A20
EISA20
£2;A20
ETA20
TFG-ALK
KIFS-AUX
Mooiea-con Ml tyrosine kinase
domain domain
www.peervoice.com/WAD870
FISH
IHC
NGS
Detection Methods
Time consuming
Expensive
Requires expertise
Widely available
Recommended by
international guidelines
Tumour or plasma
samples can be used
Multiplex reflex testing
Copyright © 2010-2024, PeerVoice
PeerVoice
Abbreviations and References
ALK Gene Rearrangement in NSCLC
Abbreviation(s): FISH: fluorescence in situ hybridisation; IHC: immunohistochemistry; NGS: next-generation sequencing.
Reference(s): Shaw AT et al. J Clin Oncol. 2009;27:4247-4253.
Soda M et al. Nature. 2007:448:561-566.
Sasaki T et al. Eur J Cancer. 2010;46:1773-1780. (ref for figure)
lonescu DN et al. Curr Oncol. 2022;29:4981-4997.
National Comprehensive Cancer Network (NCCN). Non-small cell lung cancer: Practice Guidelines.
https://www.ncenorg/professionals/physician_gls/pdf/nsclpaf. Published 14 June, 2024. Accessed 25 June, 2024.
www.peervoice.com/WAD870 Copyright © 2010-2024, PeerVoice
Abbreviations and References
ALK Gene Rearrangement in NSCLC
Abbreviation(s): FISH: fluorescence in situ hybridisation; IHC: immunohistochemistry; NGS: next-generation sequencing.
Reference(s): Shaw AT et al. J Clin Oncol. 2009;27:4247-4253.
Soda M et al. Nature. 2007:448:561-566.
Sasaki T et al. Eur J Cancer. 2010;46:1773-1780. (ref for figure)
lonescu DN et al. Curr Oncol. 2022;29:4981-4997.
National Comprehensive Cancer Network (NCCN). Non-small cell lung cancer: Practice Guidelines.
https://www.ncenorg/professionals/physician_gls/pdf/nsclpaf. Published 14 June, 2024. Accessed 25 June, 2024.
www.peervoice.com/WAD870 Copyright © 2010-2024, PeerVoice
PeerVoice
Part 2 of 4: Precision Oncology in ALK+ NSCLC:
Selecting the Right Frontline TKI-Based Treatment Modality
Raffaele Califano, MD
Honorary Professor
Division of Cancer Sciences, The University of Manchester
Consultant in Medical Oncology
The Christie NHS Foundation Trust
Manchester, United Kingdom
Copyright © 2010-2024, PeerVoice
Part 2 of 4: Precision Oncology in ALK+ NSCLC:
Selecting the Right Frontline TKI-Based Treatment Modality
Raffaele Califano, MD
Honorary Professor
Division of Cancer Sciences, The University of Manchester
Consultant in Medical Oncology
The Christie NHS Foundation Trust
Manchester, United Kingdom
Copyright © 2010-2024, PeerVoice
PeerVoice
Disclosures
Raffaele Califano, MD, has a financial interest/relationship or affiliation in the form of:
Consultant for Amgen Inc.; AstraZeneca; Bayer AG; Bristol Myers Squibb Company; Eli
Lilly and Company; F. Hoffmann-La Roche Ltd, Janssen Inc.; Merck Sharp & Dohme
Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; Sanofi; and Takeda Pharmaceutical
Company Limited.
Stock Shareholder in Supportive Care.
Advisory Board for Amgen Inc.; AstraZeneca; Bayer AG; Bristol Myers Squibb
Company; Eli Lilly and Company; F. Hoffmann-La Roche Ltd.; Janssen Inc.; Merck
Sharp & Dohme Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; Sanofi; and Takeda
Pharmaceutical Company Limited.
Grants paid to institution for conduct of clinical trials or contracted research for
AbbVie Inc.; AstraZeneca; Eli Lilly and Company; F. Hoffmann-La Roche Ltd.; Janssen
Inc.; Merck Sharp & Dohme Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; and Takeda
Pharmaceutical Company Limited.
www.peervoice.com/WAD870 Copyright © 2010-2024, PeerVoice
Disclosures
Raffaele Califano, MD, has a financial interest/relationship or affiliation in the form of:
Consultant for Amgen Inc.; AstraZeneca; Bayer AG; Bristol Myers Squibb Company; Eli
Lilly and Company; F. Hoffmann-La Roche Ltd, Janssen Inc.; Merck Sharp & Dohme
Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; Sanofi; and Takeda Pharmaceutical
Company Limited.
Stock Shareholder in Supportive Care.
Advisory Board for Amgen Inc.; AstraZeneca; Bayer AG; Bristol Myers Squibb
Company; Eli Lilly and Company; F. Hoffmann-La Roche Ltd.; Janssen Inc.; Merck
Sharp & Dohme Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; Sanofi; and Takeda
Pharmaceutical Company Limited.
Grants paid to institution for conduct of clinical trials or contracted research for
AbbVie Inc.; AstraZeneca; Eli Lilly and Company; F. Hoffmann-La Roche Ltd.; Janssen
Inc.; Merck Sharp & Dohme Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; and Takeda
Pharmaceutical Company Limited.
www.peervoice.com/WAD870 Copyright © 2010-2024, PeerVoice
PeerVoice
ALEX Trial: Efficacy
Investigator-Assessed
PFS
en = Alctini (n = 152)
= Crizotinib (n = 151)
Cumulative Incidence
of CNS Progression
PFS in Patients With CNS
Metastases at Baseline
100
— Neetinib(n = 64)
hol HR 0.43 ® a za so — Crizotinib (n = 58)
(95% C1032-058) — y ¿A TÉ mo cumulative IR
go ‘ y Eso y | ara (05%) 232-404) 2 60
40 $ 7! | 12-mo cumulative ir 40
sas À 2 9.4% (95% Cl, 54-14) on ee as
20! 10 20
o! = o ; o
mn Ts NS © o 6 2 8 24 30 Day! 3 6 9 12 15 18 21 24 27 30
Timo, mo
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Time, mo
Copyright © 2010-2024, PeerVoice
ALEX Trial: Efficacy
Investigator-Assessed
PFS
en = Alctini (n = 152)
= Crizotinib (n = 151)
Cumulative Incidence
of CNS Progression
PFS in Patients With CNS
Metastases at Baseline
100
— Neetinib(n = 64)
hol HR 0.43 ® a za so — Crizotinib (n = 58)
(95% C1032-058) — y ¿A TÉ mo cumulative IR
go ‘ y Eso y | ara (05%) 232-404) 2 60
40 $ 7! | 12-mo cumulative ir 40
sas À 2 9.4% (95% Cl, 54-14) on ee as
20! 10 20
o! = o ; o
mn Ts NS © o 6 2 8 24 30 Day! 3 6 9 12 15 18 21 24 27 30
Timo, mo
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Time, mo
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PeerVoice
LTA-1L Trial: Efficacy
BICR-Assessed PFS
Investigator-Assessed PFS
BICR-Assessed Intracranial PFS
(Primary Endpoint) (Patients With Any Baseline Brain
sé Metastases)
100 x
80 80 80
E” go = en
E Es nu Es
20 20 20
== Brgatni (n = 137) — got (n 1
o (Een ln) o Be Su ==
O 6 12 18 24 30 36 42 48 O 6 12 18 24 30 36 42 48 O 6 12 18 24 30 36 42 48 54
Time, mo Time, mo Time, mo
mPFS,mo — 3-YPFS 4-VPFS mPFS,mo 3-VPFS 4-YPFS mPFS,mo 3-YPFS 4-YPFS
(95% CI) _ (95% CI) (95% CI) (95% CI) (95%CI) (95% C1) (95%CI) (95%C1) (95% CI)
240 33 36 308 45 36 240 EJ 22
(18.5-43.2) (34-51) (26-46) (213-406) (36-54) (24-46) (29-308) (17-47) (9-39)
m 19 18 92 18 16 55 9 =
(91-13.0) (12-27) (11-26) (74-127) (1-26) (9-23) (87-75) (2-25)
HR 0.48 (95% CI 0.35-0.66);P <.0001 HR 0.43 (95% Cl, 0.31-0.58);P <.0001
HR 0.29 (95% Cl, 0.17-0.51); P <.0001
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LTA-1L Trial: Efficacy
BICR-Assessed PFS
Investigator-Assessed PFS
BICR-Assessed Intracranial PFS
(Primary Endpoint) (Patients With Any Baseline Brain
sé Metastases)
100 x
80 80 80
E” go = en
E Es nu Es
20 20 20
== Brgatni (n = 137) — got (n 1
o (Een ln) o Be Su ==
O 6 12 18 24 30 36 42 48 O 6 12 18 24 30 36 42 48 O 6 12 18 24 30 36 42 48 54
Time, mo Time, mo Time, mo
mPFS,mo — 3-YPFS 4-VPFS mPFS,mo 3-VPFS 4-YPFS mPFS,mo 3-YPFS 4-YPFS
(95% CI) _ (95% CI) (95% CI) (95% CI) (95%CI) (95% C1) (95%CI) (95%C1) (95% CI)
240 33 36 308 45 36 240 EJ 22
(18.5-43.2) (34-51) (26-46) (213-406) (36-54) (24-46) (29-308) (17-47) (9-39)
m 19 18 92 18 16 55 9 =
(91-13.0) (12-27) (11-26) (74-127) (1-26) (9-23) (87-75) (2-25)
HR 0.48 (95% CI 0.35-0.66);P <.0001 HR 0.43 (95% Cl, 0.31-0.58);P <.0001
HR 0.29 (95% Cl, 0.17-0.51); P <.0001
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CROWN Trial: Efficacy
Investigator-Assessed PFS Investigator-Assessed Intracranial Progression
(Patients With Baseline Brain Metastases)
100 — Lorlatinib (n = 149) — Lorlatinib (n = 35)
— Crizotinib (n = 38)
— Crizotinib (n = 147)
O 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 9:4 6 1102022 20090404448 628608408 72 7800
Time, mo Time, mo
ER PFS, mo (65% Ci Median Time to Intracranial
Neta PPM (GEN) Events,n Progression, mo (95% CI)
55 NR (64.3-NR) 5 NR (NR-NR)
15 9.1(7.4-10.9) 26 72(37-10)
HR 0.19 (95% Cl, 0.13-0.27) HR 0.03 (95% Cl 0.01-0.13)
www.peervoice.com/WAD870 Copyright © 2010-2024, PeerVoice
CROWN Trial: Efficacy
Investigator-Assessed PFS Investigator-Assessed Intracranial Progression
(Patients With Baseline Brain Metastases)
100 — Lorlatinib (n = 149) — Lorlatinib (n = 35)
— Crizotinib (n = 38)
— Crizotinib (n = 147)
O 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 9:4 6 1102022 20090404448 628608408 72 7800
Time, mo Time, mo
ER PFS, mo (65% Ci Median Time to Intracranial
Neta PPM (GEN) Events,n Progression, mo (95% CI)
55 NR (64.3-NR) 5 NR (NR-NR)
15 9.1(7.4-10.9) 26 72(37-10)
HR 0.19 (95% Cl, 0.13-0.27) HR 0.03 (95% Cl 0.01-0.13)
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Summary of Efficacy Data for TKis
CNS
Agent Trial N Metastases ORR, %
at Baseline, %
PFS in ITT Intracranial
Population, mo ORR, %
Alectinib: 42.1°° Alectinib: 82.9°
Crizotinib: 38.4°° Crizotinib: 75.5°
Alectinib: 814
Alectinib ALEX 303 Crizotinib: 50°4
Brigatinib: 29.144 Brigatinib: 744
Crizotinib: 29.734 Crizotinib: 624
Brigatinib: 7864
FEA ALTA-IL 275 Crizotinib: 26b4
Crizotinib: 9.20
(HR 0.43)
Lorlatinib: NR°
Lorlatinib: 23.4°° Lorlatinib: 81° Crizotinib: 9.1 Lorlatinib: 60*<
Crizotinib: 25.8°° Crizotinib: 63° (HR 0.19 [95% Cl, Crizotinib: 11°
0.13-0.27])e
® Measurable and/or non-measurable CNS lesions at baseline. ? Measurable CNS lesions at baseline. Investigator-assessed.
SBICR-assessed.
This information is presented for illustrative purposes only and is not a direct comparison of trial data. Cross-trial
IEA CROWN 296
comparisons are potentially confounded by differences in trial design and study population.
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Summary of Efficacy Data for TKis
CNS
Agent Trial N Metastases ORR, %
at Baseline, %
PFS in ITT Intracranial
Population, mo ORR, %
Alectinib: 42.1°° Alectinib: 82.9°
Crizotinib: 38.4°° Crizotinib: 75.5°
Alectinib: 814
Alectinib ALEX 303 Crizotinib: 50°4
Brigatinib: 29.144 Brigatinib: 744
Crizotinib: 29.734 Crizotinib: 624
Brigatinib: 7864
FEA ALTA-IL 275 Crizotinib: 26b4
Crizotinib: 9.20
(HR 0.43)
Lorlatinib: NR°
Lorlatinib: 23.4°° Lorlatinib: 81° Crizotinib: 9.1 Lorlatinib: 60*<
Crizotinib: 25.8°° Crizotinib: 63° (HR 0.19 [95% Cl, Crizotinib: 11°
0.13-0.27])e
® Measurable and/or non-measurable CNS lesions at baseline. ? Measurable CNS lesions at baseline. Investigator-assessed.
SBICR-assessed.
This information is presented for illustrative purposes only and is not a direct comparison of trial data. Cross-trial
IEA CROWN 296
comparisons are potentially confounded by differences in trial design and study population.
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Summary of Safety Data for TKls
A. Serious Dose Treatment
Agent us AEs,% Reduction, % Discontinuation, % _ Most Common AEs
Anaemia, myalgia,
er Alectinib: 13.2 bilirubin, weight gain,
Alectinib ALEX Crizotinib: 13.2 joint pain,
photosensitivity reaction
ALTA-IL Brigatinib: N/A — Brigatinib: 44 Brigatini 1 o Ce ibe:
Crizotinib: N/A Crizotinib: 25 early onset ILD/
. “ pneumonitis
Hypercholesterolaemia,
i“ an hypertriglyceridaemia,
Lorlatinib CROWN ee ee weight gain, oedema,
izotinib: iizotinib: peripheral, neuropathy,
cognitive effects*
® Higher incidence of all-causality grade 3/4 AEs in patients in the lorlatinib group vs crizotinib group was largely due to
hypertriglyceridaemia (25% vs 0%), hypercholesterolaemia (21% vs 0%), weight gain (23% vs 2%), and hypertension (12% v 1%).
This information is presented for illustrative purposes only and is not a direct comparison of trial data. Cross-trial
comparisons are potentially confounded by differences in trial design and study population.
www.peervoice.com/WAD870 Copyright © 2010-2024, PeerVoice
Summary of Safety Data for TKls
A. Serious Dose Treatment
Agent us AEs,% Reduction, % Discontinuation, % _ Most Common AEs
Anaemia, myalgia,
er Alectinib: 13.2 bilirubin, weight gain,
Alectinib ALEX Crizotinib: 13.2 joint pain,
photosensitivity reaction
ALTA-IL Brigatinib: N/A — Brigatinib: 44 Brigatini 1 o Ce ibe:
Crizotinib: N/A Crizotinib: 25 early onset ILD/
. “ pneumonitis
Hypercholesterolaemia,
i“ an hypertriglyceridaemia,
Lorlatinib CROWN ee ee weight gain, oedema,
izotinib: iizotinib: peripheral, neuropathy,
cognitive effects*
® Higher incidence of all-causality grade 3/4 AEs in patients in the lorlatinib group vs crizotinib group was largely due to
hypertriglyceridaemia (25% vs 0%), hypercholesterolaemia (21% vs 0%), weight gain (23% vs 2%), and hypertension (12% v 1%).
This information is presented for illustrative purposes only and is not a direct comparison of trial data. Cross-trial
comparisons are potentially confounded by differences in trial design and study population.
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Abbreviations and References
ALEX Trial: Efficacy
Abbreviation(s): CNS: central nervous system; IR: incidence rate; NE: not evaluable; PFS: progression-free survival.
Reference(s): Peters S et al. N Engl J Med. 2017;377:829-838.
Camidge DR et al. J Thorac Oncol. 2019;14:1233-1243.
ALTA-IL Trial: Efficacy
Abbreviation(s): BICR: blinded independent central review; mPFS: median PFS.
Reference(s): Camidge DR et al. J Thorac Oncol. 2021;16:2091-2108.
CROWN Trial: Efficacy
Abbreviation(s): NR: not reached.
Reference(s): Solomon BJ et al. J Clin Oncol. 2024 May 31 [Epub ahead of print]. doi: 10.1200/JCO.24.00581
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Abbreviations and References
ALEX Trial: Efficacy
Abbreviation(s): CNS: central nervous system; IR: incidence rate; NE: not evaluable; PFS: progression-free survival.
Reference(s): Peters S et al. N Engl J Med. 2017;377:829-838.
Camidge DR et al. J Thorac Oncol. 2019;14:1233-1243.
ALTA-IL Trial: Efficacy
Abbreviation(s): BICR: blinded independent central review; mPFS: median PFS.
Reference(s): Camidge DR et al. J Thorac Oncol. 2021;16:2091-2108.
CROWN Trial: Efficacy
Abbreviation(s): NR: not reached.
Reference(s): Solomon BJ et al. J Clin Oncol. 2024 May 31 [Epub ahead of print]. doi: 10.1200/JCO.24.00581
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Abbreviations and References (Cont'd)
Summary of Efficacy Data for TKIs
Abbreviation(s): ITT: intention-to-treat; ORR: objective response rate; TKI: tyrosine kinase inhibitor.
Reference(s): Peters S et al. N Engl J Med. 2017;377:829-838.
Camidge DR et al. J Thorac Oncol. 2019;14:1233-1243.
Camidge DR et al. J Thorac Oncol. . 20: 3
Solomon BJ et al. J Clin Oncol. 2024 May 31 [Epub ahead of print]. doi: 10.1200/JC0.24.00581.
Summary of Safety Data for TKIs
Abbreviation(s): CK: creatine kinase; HBP: high blood pressure; ILD: interstitial lung disease.
Reference(s): Peters S et al. N Engl J Med. 2017;377:829-838.
Camidge DR et al. J Thorac Oncol. 2019;14:1233-1243.
Camidge DR et al. J Thorac Oncol. 2021;16:2091-2108.
Solomon BJ et al. J Clin Oncol. 2024 May 31 [Epub ahead of print]. doi: 10.1200/JC0.24.00581.
www.peervoice.com/WAD870 Copyright © 2010-2024, PeerVoice
Abbreviations and References (Cont'd)
Summary of Efficacy Data for TKIs
Abbreviation(s): ITT: intention-to-treat; ORR: objective response rate; TKI: tyrosine kinase inhibitor.
Reference(s): Peters S et al. N Engl J Med. 2017;377:829-838.
Camidge DR et al. J Thorac Oncol. 2019;14:1233-1243.
Camidge DR et al. J Thorac Oncol. . 20: 3
Solomon BJ et al. J Clin Oncol. 2024 May 31 [Epub ahead of print]. doi: 10.1200/JC0.24.00581.
Summary of Safety Data for TKIs
Abbreviation(s): CK: creatine kinase; HBP: high blood pressure; ILD: interstitial lung disease.
Reference(s): Peters S et al. N Engl J Med. 2017;377:829-838.
Camidge DR et al. J Thorac Oncol. 2019;14:1233-1243.
Camidge DR et al. J Thorac Oncol. 2021;16:2091-2108.
Solomon BJ et al. J Clin Oncol. 2024 May 31 [Epub ahead of print]. doi: 10.1200/JC0.24.00581.
www.peervoice.com/WAD870 Copyright © 2010-2024, PeerVoice
PeerVoice
Part 3 of 4: TKI Therapy in Practice: Rapid Run Down
of Practical Considerations for Optimal Use
Raffaele Califano, MD
Honorary Professor
Division of Cancer Sciences, The University of Manchester
Consultant in Medical Oncology
The Christie NHS Foundation Trust
Manchester, United Kingdom
Copyright © 2010-2024, PeerVoice
Part 3 of 4: TKI Therapy in Practice: Rapid Run Down
of Practical Considerations for Optimal Use
Raffaele Califano, MD
Honorary Professor
Division of Cancer Sciences, The University of Manchester
Consultant in Medical Oncology
The Christie NHS Foundation Trust
Manchester, United Kingdom
Copyright © 2010-2024, PeerVoice
PeerVoice
Disclosures
Raffaele Califano, MD, has a financial interest/relationship or affiliation in the form of:
Consultant for Amgen Inc.; AstraZeneca; Bayer AG; Bristol Myers Squibb Company; Eli
Lilly and Company; F. Hoffmann-La Roche Ltd, Janssen Inc.; Merck Sharp & Dohme
Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; Sanofi; and Takeda Pharmaceutical
Company Limited.
Stock Shareholder in Supportive Care.
Advisory Board for Amgen Inc.; AstraZeneca; Bayer AG; Bristol Myers Squibb
Company; Eli Lilly and Company; F. Hoffmann-La Roche Ltd.; Janssen Inc.; Merck
Sharp & Dohme Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; Sanofi; and Takeda
Pharmaceutical Company Limited.
Grants paid to institution for conduct of clinical trials or contracted research for
AbbVie Inc.; AstraZeneca; Eli Lilly and Company; F. Hoffmann-La Roche Ltd.; Janssen
Inc.; Merck Sharp & Dohme Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; and Takeda
Pharmaceutical Company Limited.
www.peervoice.com/WAD870 Copyright © 2010-2024, PeerVoice
Disclosures
Raffaele Califano, MD, has a financial interest/relationship or affiliation in the form of:
Consultant for Amgen Inc.; AstraZeneca; Bayer AG; Bristol Myers Squibb Company; Eli
Lilly and Company; F. Hoffmann-La Roche Ltd, Janssen Inc.; Merck Sharp & Dohme
Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; Sanofi; and Takeda Pharmaceutical
Company Limited.
Stock Shareholder in Supportive Care.
Advisory Board for Amgen Inc.; AstraZeneca; Bayer AG; Bristol Myers Squibb
Company; Eli Lilly and Company; F. Hoffmann-La Roche Ltd.; Janssen Inc.; Merck
Sharp & Dohme Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; Sanofi; and Takeda
Pharmaceutical Company Limited.
Grants paid to institution for conduct of clinical trials or contracted research for
AbbVie Inc.; AstraZeneca; Eli Lilly and Company; F. Hoffmann-La Roche Ltd.; Janssen
Inc.; Merck Sharp & Dohme Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; and Takeda
Pharmaceutical Company Limited.
www.peervoice.com/WAD870 Copyright © 2010-2024, PeerVoice
PeerVoice
Considerations for Initiating TKI Therapy
Agent
Crizotinib
Ceritinib
Alectinib
Brigatinib
Lorlatinib
Dosing Pill Burden CYP-Related Drug Interactions
250 mg orally BID Strong or moderate CYP3A inhibitors
(500 mg daily), taken 2 pills/day Strong CYP3A inducers
continuously CYP3A substrates
450 mg orally QD with en om
à ás Strong CYP3A inhibitors/inducers
food, at the same time 3 pills/day
each day CYP3A and CYP2C9 substrates
600 mg orally BID Ash No clinically meaningful drug interactions
(1200 mg daily), with food La U observed in clinical studies with alectinib
7 days run-in at 90 mg QD, E Strong CYP3A inhibitors/inducers
then 180 mg QD, 1 pill/day Ces subermas
with or without food
Known strong CYP3A inhibitors/ inducers
100 mg QD 1 pill/day Known P-gp substrates with a narrow
therapeutic index
www.peervoice.com/WADB70
Copyright © 2010-2024, PeerVoice
Considerations for Initiating TKI Therapy
Agent
Crizotinib
Ceritinib
Alectinib
Brigatinib
Lorlatinib
Dosing Pill Burden CYP-Related Drug Interactions
250 mg orally BID Strong or moderate CYP3A inhibitors
(500 mg daily), taken 2 pills/day Strong CYP3A inducers
continuously CYP3A substrates
450 mg orally QD with en om
à ás Strong CYP3A inhibitors/inducers
food, at the same time 3 pills/day
each day CYP3A and CYP2C9 substrates
600 mg orally BID Ash No clinically meaningful drug interactions
(1200 mg daily), with food La U observed in clinical studies with alectinib
7 days run-in at 90 mg QD, E Strong CYP3A inhibitors/inducers
then 180 mg QD, 1 pill/day Ces subermas
with or without food
Known strong CYP3A inhibitors/ inducers
100 mg QD 1 pill/day Known P-gp substrates with a narrow
therapeutic index
www.peervoice.com/WADB70
Copyright © 2010-2024, PeerVoice
PeerVoice
Managing AEs Through Shared
Patients should be
fully informed and ier houle
choosing an agent immediately re
Alectinib, brigatinib,
and lorlatinib have
very different
should be part of a
shared decision-
making process
safety profiles and
AEs may occur
+ Supportive medications can be sufficient for some AEs,
while others should be managed aggressively and quickly
«ILD/pneumonitis: Imaging and pulmonary function testing
to evaluate; steroids or treatment discontinuation may be
required
«Monitor for cardiovascular AEs with ECG at baseline,
renal/hepatic function, and electrolyte abnormalities
Copyright © 2010-2024, Peervoice
Managing AEs Through Shared
Patients should be
fully informed and ier houle
choosing an agent immediately re
Alectinib, brigatinib,
and lorlatinib have
very different
should be part of a
shared decision-
making process
safety profiles and
AEs may occur
+ Supportive medications can be sufficient for some AEs,
while others should be managed aggressively and quickly
«ILD/pneumonitis: Imaging and pulmonary function testing
to evaluate; steroids or treatment discontinuation may be
required
«Monitor for cardiovascular AEs with ECG at baseline,
renal/hepatic function, and electrolyte abnormalities
Copyright © 2010-2024, Peervoice
PeerVoice
Abbreviations and References
Considerations for Initiating TKI Therapy
Abbreviation(s): P-gp: permeability glycoprotein; TKI: tyrosine kinase inhibitor.
Reference(s): Crizotinib: US Prescribing Information (PI).
https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217581s000Iblpdf. Accessed 4 July, 2024.
itinib: US Pl. https://www.accessdata fda gov/drugsattda_docs/label/2017/205755s009lbl pdf. Accessed 4 July,
Alectinib: US PI. https://www.accessdatafda.gov/drugsatfda_docs/label/2024/208434s015lbl.pdf. Accessed 4 July,
2024.
Brigatinib: US Pl. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/208772s018lbLpdf. Accessed 4 July,
2024.
Lorlatinib: US PL https://www.accessdata.fdagov/drugsatfda_docs/label/2021/210868s004lbl.pdf. Accessed 4 July,
2024,
Managing AEs Through Shared Decision-Making
Abbreviation(s): ILD: interstitial lung disease.
Reference(s): PeerVoice Activity; Raffaele Califano, MD; June 2024.
www.peervoice.com/WAD870 Copyright © 2010-2024, PeerVoice
Abbreviations and References
Considerations for Initiating TKI Therapy
Abbreviation(s): P-gp: permeability glycoprotein; TKI: tyrosine kinase inhibitor.
Reference(s): Crizotinib: US Prescribing Information (PI).
https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217581s000Iblpdf. Accessed 4 July, 2024.
itinib: US Pl. https://www.accessdata fda gov/drugsattda_docs/label/2017/205755s009lbl pdf. Accessed 4 July,
Alectinib: US PI. https://www.accessdatafda.gov/drugsatfda_docs/label/2024/208434s015lbl.pdf. Accessed 4 July,
2024.
Brigatinib: US Pl. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/208772s018lbLpdf. Accessed 4 July,
2024.
Lorlatinib: US PL https://www.accessdata.fdagov/drugsatfda_docs/label/2021/210868s004lbl.pdf. Accessed 4 July,
2024,
Managing AEs Through Shared Decision-Making
Abbreviation(s): ILD: interstitial lung disease.
Reference(s): PeerVoice Activity; Raffaele Califano, MD; June 2024.
www.peervoice.com/WAD870 Copyright © 2010-2024, PeerVoice
PeerVoice
Part 4 of 4: Metastasis Matters: Maximising Outcomes for Patients
With ALK+ NSCLC and CNS Metastases
Raffaele Califano, MD
Honorary Professor
Division of Cancer Sciences, The University of Manchester
Consultant in Medical Oncology
The Christie NHS Foundation Trust
Manchester, United Kingdom
Copyright © 2010-2024, PeerVoice
Part 4 of 4: Metastasis Matters: Maximising Outcomes for Patients
With ALK+ NSCLC and CNS Metastases
Raffaele Califano, MD
Honorary Professor
Division of Cancer Sciences, The University of Manchester
Consultant in Medical Oncology
The Christie NHS Foundation Trust
Manchester, United Kingdom
Copyright © 2010-2024, PeerVoice
PeerVoice
Disclosures
Raffaele Califano, MD, has a financial interest/relationship or affiliation in the form of:
Consultant for Amgen Inc.; AstraZeneca; Bayer AG; Bristol Myers Squibb Company; Eli
Lilly and Company; F. Hoffmann-La Roche Ltd, Janssen Inc.; Merck Sharp & Dohme
Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; Sanofi; and Takeda Pharmaceutical
Company Limited.
Stock Shareholder in Supportive Care.
Advisory Board for Amgen Inc.; AstraZeneca; Bayer AG; Bristol Myers Squibb
Company; Eli Lilly and Company; F. Hoffmann-La Roche Ltd.; Janssen Inc.; Merck
Sharp & Dohme Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; Sanofi; and Takeda
Pharmaceutical Company Limited.
Grants paid to institution for conduct of clinical trials or contracted research for
AbbVie Inc.; AstraZeneca; Eli Lilly and Company; F. Hoffmann-La Roche Ltd.; Janssen
Inc.; Merck Sharp & Dohme Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; and Takeda
Pharmaceutical Company Limited.
www.peervoice.com/WAD870 Copyright © 2010-2024, PeerVoice
Disclosures
Raffaele Califano, MD, has a financial interest/relationship or affiliation in the form of:
Consultant for Amgen Inc.; AstraZeneca; Bayer AG; Bristol Myers Squibb Company; Eli
Lilly and Company; F. Hoffmann-La Roche Ltd, Janssen Inc.; Merck Sharp & Dohme
Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; Sanofi; and Takeda Pharmaceutical
Company Limited.
Stock Shareholder in Supportive Care.
Advisory Board for Amgen Inc.; AstraZeneca; Bayer AG; Bristol Myers Squibb
Company; Eli Lilly and Company; F. Hoffmann-La Roche Ltd.; Janssen Inc.; Merck
Sharp & Dohme Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; Sanofi; and Takeda
Pharmaceutical Company Limited.
Grants paid to institution for conduct of clinical trials or contracted research for
AbbVie Inc.; AstraZeneca; Eli Lilly and Company; F. Hoffmann-La Roche Ltd.; Janssen
Inc.; Merck Sharp & Dohme Corp.; Novartis AG; Pfizer Inc.; PharmaMar S.A.; and Takeda
Pharmaceutical Company Limited.
www.peervoice.com/WAD870 Copyright © 2010-2024, PeerVoice
PeerVoice
ctivity of TKIs
In the Clinical Trials
What size was used to define a measurable lesion?
Measurable vs non-measurable lesions?
Were patients stratified by baseline CNS metastases?
www.peervoice.com/WAD870 Copyright © 2010-2024, PeerVoice
ctivity of TKIs
In the Clinical Trials
What size was used to define a measurable lesion?
Measurable vs non-measurable lesions?
Were patients stratified by baseline CNS metastases?
www.peervoice.com/WAD870 Copyright © 2010-2024, PeerVoice
PeerVoice
Abbreviations and References
Evaluating CNS Activity of TKis
Abbreviation(s): CNS: central nervous system; Tl: tyrosine kinase inhibitor.
www.peervoice.com/WAD870 Copyright © 2010-2024, PeerVoice
Abbreviations and References
Evaluating CNS Activity of TKis
Abbreviation(s): CNS: central nervous system; Tl: tyrosine kinase inhibitor.
www.peervoice.com/WAD870 Copyright © 2010-2024, PeerVoice
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