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alki in nsclc

Dec 12, 202315 min read

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🌱 來自: ALK

alki in nsclc

KFSYSCC Fellowship Tuesday Morning Journal Club

2023-12-12

Treatment of
ALK Translocation-Positive
Non-Small Cell Lung Cancer


(1)Presenter, 專研醫師, 和信治癌中心醫院腫瘤內科部

(2)Moderator, 主治醫師, 和信治癌中心醫院腫瘤內科部

Outline

  • Clinical Scenario
  • Introduction to ALK mutation
  • Current ALK treatment landscape
    • Crizotinib
    • Alectinib
    • Brigatinib
    • Lorlatiib
      • Lorlatiib toxicity
  • ALKi resistance
  • Take home messages

Clinical
Scenario

Patient 1 58-year-old man

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  • Lung cancer, RML,
  • Adenocarcinoma,
  • acinar predominant with pleural mets,
  • s/p wedge resection on 2017/09/26 (義大)
  • pT4NXM1a
  • EGFR mutation(-), ALK(+) :::split

Treatment course

  • crizotinib
    • PD in 6 month
  • pemetrexed / carboplatin
  • alectinib 2018~Now
    • SD :::

ID: 05682406

Patient 2: 49-year-old man

  • Lung cancer, Adenocarcinoma, RLL, cT3N3M1c with lung-lung and brain metastases and pleural seedings, EGFR(-), ALK(+), ROS1(-), s/p alectinib, stable disease

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Increasing number of FDA-approved drugs for treatment of oncogene-addicted NSCLC

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Delahaye C, Figarol S, Pradines A, Favre G, Mazieres J, Calvayrac O. Early Steps of Resistance to Targeted Therapies in Non-Small-Cell Lung Cancer. Cancers. 2022;14(11):2613. doi:10.3390/cancers14112613

What is ALK?

Anaplastic lymphoma kinase and ALK inhibitors

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Huang H. Anaplastic Lymphoma Kinase (ALK) Receptor Tyrosine Kinase: A Catalytic Receptor with Many Faces. International Journal of Molecular Sciences. 2018;19(11):3448. doi:10.3390/ijms19113448

Domain structure of receptor tyrosine kinase families

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Hallberg B, Palmer RH. Crizotinib - Latest Champion in the Cancer Wars? New England Journal of Medicine. 2010;363(18):1760-1762. doi:10.1056/NEJMe1010404

Gene fusion between EML4 and ALK

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Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448(7153):561-566. doi:10.1038/nature05945

Signaling Pathways Activated by ALK Fusion Proteins

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Hallberg B, Palmer RH. Crizotinib - Latest Champion in the Cancer Wars? New England Journal of Medicine. 2010;363(18):1760-1762. doi:10.1056/NEJMe1010404

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Schneider JL, Lin JJ, Shaw AT. ALK-positive lung cancer: a moving target. Nat Cancer. 2023;4(3):330-343. doi:10.1038/s43018-023-00515-0

Therapeutic Sequencing in ALK NSCLC

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Elsayed M, Christopoulos P. Therapeutic Sequencing in ALK+ NSCLC. Pharmaceuticals. 2021;14(2):80. doi:10.3390/ph14020080

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Crizotinib

1st generation ALKi

First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer


:::columns 1. Design: - Phase 3 trial, Open-label - Multicenter, Randomized 2. 343 patients 3. Patients characteristics: - Advanced ALK-positive NSCLC - no previous systemic treatment :::split 4. Agent: - crizotinib (250 mg twice daily) in a 3-week cycle - pemetrexed (500 mg per square meter of body-surface area) or docetaxel (75 mg per square meter) every 3 weeks. 5. First-line treatment for advanced ALK-positive non-small-cell lung cancer 6. Trial Name: PROFILE 1014 ::: > Solomon BJ, Mok T, Kim DW, et al. First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer. New England Journal of Medicine. 2014;371(23):2167-2177. doi:10.1056/NEJMoa1408440 ---

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OutcomeCrizotinibChemotherapy
PFS (median)10.9 months7.0 months
Response rate74%45%
HR for progression or death0.45-
Hazard ratio for death0.82-

Solomon BJ, Mok T, Kim DW, et al. First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer. New England Journal of Medicine. 2014;371(23):2167-2177. doi:10.1056/NEJMoa1408440

Crizotinib in ROS1-Rearranged Non-Small-Cell Lung Cancer

:::free Median progression-free survival was 19.2 months Figure: height:450px :::split

  • 50 patients
  • Dx by NGS
  • phase 1
  • ORR: 72% :::

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圍毆 - 梗圖產生 ↪ 器 (手工模式) . Accessed November 28, 2023. https://memes.tw/maker/painter/742

Alectinib

2nd generation of ALKi

ALEX, J-ALEX, ALESIA, ALUR

Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer

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  • Phase 3, Open-label
  • Multicenter, Randomized
  • 303 patients, 1:1
    • untreated, advanced ALK+ NSCLC
    • including those with asx CNS disease
  • Agent:
    • Alectinib 600 mg BID
    • Crizotinib 250 mg BID

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OutcomeAlectinibCrizotinib
Investigator-assessed PFS (median)Not reached-
12-month event-free survival rate68.4%48.7%
Hazard ratio for disease progression or death0.47-
Time to CNS progression (cause-specific HR)0.16-
Objective response rate82.9%75.5%
Grade 3 to 5 adverse events41%50%

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Peters S, Camidge DR, Shaw AT, et al. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. New England Journal of Medicine. 2017;377(9):829-838. doi:10.1056/NEJMoa1704795

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Peters S, Camidge DR, Shaw AT, et al. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. New England Journal of Medicine. 2017;377(9):829-838. doi:10.1056/NEJMoa1704795

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Peters S, Camidge DR, Shaw AT, et al. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. New England Journal of Medicine. 2017;377(9):829-838. doi:10.1056/NEJMoa1704795

Alectinib vs crizotinib in ALK+ NSCLC (J-ALEX):
an open-label, randomised phase 3 trial

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  • Multi-center trial conducted in Japan
  • 103 vs 104 patients
  • Chemotherapy-naive or had received one previous chemotherapy regimen
  • Agents:
    • alectinib 300 mg BID
    • crizotinib 250 mg BID
  • Primary endpoint: PFS :::split | Outcome | Alectinib | Crizotinib | | ---------------------------------------- | ------------------------- | ----------------------------- | | Median PFS | Not estimated | 10.2 months (95% CI 8.2-12.0) | | Hazard ratio | 0.34 (99.7% CI 0.17-0.71) | - | | Grade 3 or 4 adverse events | 27 (26%) of 103 | 54 (52%) of 104 | | Dose interruptions due to adverse events | 30 (29%) of 103 | 77 (74%) of 104 | | DC of study drug due to AEs | 9 (9%) | 21 (20%) |
  • Alectinib dose (300 mg twice daily) is lower than the approved dose in countries other than Japan :::

Hida T, Nokihara H, Kondo M, et al. Alectinib versus crizotinib in patients with ALK -positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. The Lancet. 2017;390(10089):29-39. doi:10.1016/S0140-6736(17)30565-2

(A), by line of treatment (B), and by disease stage (C). Hazard ratios were estimated by a stratified Cox analysis

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Hida T, Nokihara H, Kondo M, et al. Alectinib versus crizotinib in patients with ALK -positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. The Lancet. 2017;390(10089):29-39. doi:10.1016/S0140-6736(17)30565-2

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Alectinib versus crizotinib in untreated Asian patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer (ALESIA)

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  1. Design:
  • Phase 3, Randomized
  • Open-label,
  • Recruiting only Asian: China, South Korea, and Thailand
  1. Number of patients: 187
    • Asian patients
    • asymptomatic CNS metastases were permitted

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  1. Agent:
  • Alectinib (600 mg twice per day)
  • Crizotinib (250 mg)

  1. Treatment line: First-line treatment for ALK-positive non-small-cell lung cancer

  2. Trial Name or NCT Number: NCT02838420

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Zhou C, Kim SW, Reungwetwattana T, et al. Alectinib versus crizotinib in untreated Asian patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer (ALESIA): a randomised phase 3 study. The Lancet Respiratory Medicine. 2019;7(5):437-446. doi:10.1016/S2213-2600(19)30053-0

  1. Comparison of two groups: | Endpoint | Alectinib | Crizotinib | | -------------------------------------------------------------------------- | ----------------------------------- | --------------------------------------- | | Investigator-assessed progression-free survival | HR 0·22, 95% CI 0·13-0·38, p<0·0001 | Median PFS not estimable vs 11·1 months | | Independent review committee-assessed progression-free survival | HR 0·37, 0·22-0·61, p<0·0001 | Not reported | | Objective response | 91% of 125 | 77% of 62 | | Duration of response | HR 0·22, 95% CI 0·12-0·40, p<0·0001 | Not reported | | Time to CNS progression | Cause-specific HR 0·14 | Not reported | | CNS objective response (measurable or non-measurable baseline CNS lesions) | 73% of 44 patients | 22% of 23 patients | | Grade 3-5 adverse events | 29% of 125 | 48% of 62 | | Serious adverse events | 15% of 125 | 26% of 62 |

Zhou C, Kim SW, Reungwetwattana T, et al. Alectinib versus crizotinib in untreated Asian patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer (ALESIA): a randomised phase 3 study. The Lancet Respiratory Medicine. 2019;7(5):437-446. doi:10.1016/S2213-2600(19)30053-0

OS

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Zhou C, Kim SW, Reungwetwattana T, et al. Alectinib versus crizotinib in untreated Asian patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer (ALESIA): a randomised phase 3 study. The Lancet Respiratory Medicine. 2019;7(5):437-446. doi:10.1016/S2213-2600(19)30053-0

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Zhou C, Kim SW, Reungwetwattana T, et al. Alectinib versus crizotinib in untreated Asian patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer (ALESIA): a randomised phase 3 study. The Lancet Respiratory Medicine. 2019;7(5):437-446. doi:10.1016/S2213-2600(19)30053-0

Alectinib versus chemotherapy in crizotinib pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer

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  1. Design:
  • Trial phase: III, Multi-center
  • Randomized, Open-label
  1. Number of patients: 107
    • Advanced/metastatic ALK-positive non-small-cell lung cancer patients
    • Previously treated with platinum-based doublet chemotherapy and crizotinib

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  1. Agent:
  • Alectinib 600 mg twice daily
  • or chemotherapy (pemetrexed 500 mg/m2 or docetaxel 75 mg/m2, both every 3 weeks)

  1. Treatment line: Patients who have progressed on, or were intolerant to, crizotinib

  2. Trial Name or NCT Number: ALUR, NCT02604342

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Novello S, Mazières J, Oh IJ, et al. Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study. Ann Oncol. 2018;29(6):1409-1416. doi:10.1093/annonc/mdy121

Outcome

OutcomeAlectinibChemotherapy
PFS by investigator assessment,9.6 months (95% CI:6.9-12.2)1.4 months (95% CI:1.3-1.6)
PFS by Independent Review Committee assessment7.1 months (95% CI:6.3-10.8)1.6 months (95% CI:1.3-4.1)
CNS ORR54.2%0%
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Novello S, Mazières J, Oh IJ, et al. Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study. Ann Oncol. 2018;29(6):1409-1416. doi:10.1093/annonc/mdy121

Brigatinib

2nd generation ALKi

ALTA-1L, ALTA-2L

Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer

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  • phase III, Open-label
  • Randomized
  • 275 patients, 1:1
    • Advanced ALK-positive NSCLC patients
    • not previously received ALK inhibitors
  • Brigatinib 180 mg QD
    • 7-day lead-in period at 90 mg
  • Crizotinib 250 mg BID :::split | Outcome | Brigatinib | Crizotinib | | ------------------ | ---------------------- | ---------------------- | | Estimated 12m PFS: | 67% (95% CI, 56 to 75) | 43% (95% CI, 32 to 53) | | ORR | 71% (95% CI, 62 to 78) | 60% (95% CI, 51 to 68) | | Intracranial RR | 78% (95% CI, 52 to 94) | 29% (95% CI, 11 to 52) |
  • Trial: ALTA-1L NCT02737501 :::

Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer. New England Journal of Medicine. 2018;379(21):2027-2039. doi:10.1056/NEJMoa1810171

Outcome

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Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer. New England Journal of Medicine. 2018;379(21):2027-2039. doi:10.1056/NEJMoa1810171

Survival without intracranial disease progression with brain metastasis at baseline

:::free Figure: height:450px :::split the confirmed rate of intracranial response among patients with measurable lesions was 78% (95% CI, 52 to 94) and 29% (95% CI, 11 to 52), respectively. :::

Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer. New England Journal of Medicine. 2018;379(21):2027-2039. doi:10.1056/NEJMoa1810171

Brigatinib in Patients With Advanced ALK-Positive NSCLC Who Progressed on Alectinib or Ceritinib

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!!!note Median PFS 3.8 in this Phase 2 trial

Ou SHI, Nishio M, Ahn MJ, et al. Efficacy of Brigatinib in Patients With Advanced ALK-Positive NSCLC Who Progressed on Alectinib or Ceritinib: ALK in Lung Cancer Trial of brigAtinib-2 (ALTA-2). Journal of Thoracic Oncology. 2022;17(12):1404-1414. doi:10.1016/j.jtho.2022.08.018

In this study: ALK fusion and EML4 fusion detected at baseline in patients receiving previous alectinib or previous ceritinib

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Ou SHI, Nishio M, Ahn MJ, et al. Efficacy of Brigatinib in Patients With Advanced ALK-Positive NSCLC Who Progressed on Alectinib or Ceritinib: ALK in Lung Cancer Trial of brigAtinib-2 (ALTA-2). Journal of Thoracic Oncology. 2022;17(12):1404-1414. doi:10.1016/j.jtho.2022.08.018

Brigatinib Versus Alectinib in ALK-Positive NSCLC After Disease Progression on Crizotinib: Results of Phase 3 ALTA-3 Trial

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Brigatinib was not superior to alectinib for PFS in crizotinib-pretreated ALK+ NSCLC

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Yang JCH, Liu G, Lu S, et al. Brigatinib Versus Alectinib in ALK-Positive NSCLC After Disease Progression on Crizotinib: Results of Phase 3 ALTA-3 Trial. Journal of Thoracic Oncology. 2023;18(12):1743-1755. doi:10.1016/j.jtho.2023.08.010

Ceritinib

Yet another 2nd generation ALKi

ASCEND-5

First-line ceritinib versus platinum-based chemotherapy

ASCEND-4

  • Design: Randomized, open-label, phase 3 trial involving 134 centers across 28 countries.
  • Number of patients: 376 patients were randomly assigned to ceritinib (n=189) or chemotherapy (n=187).
  • Patients characteristics: Untreated patients with stage IIIB/IV ALK-rearranged non-squamous NSCLC.
  • Agent: Oral ceritinib 750 mg/day or platinum-based chemotherapy ([cisplatin 75 mg/m2 or carboplatin AUC 5-6 plus pemetrexed 500 mg/m2] every 3 weeks for four cycles followed by maintenance pemetrexed).
  • Treatment line: First-line treatment.

Soria JC, Tan DSW, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK -rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. The Lancet. 2017;389(10072):917-929. doi:10.1016/S0140-6736(17)30123-X

First-line ceritinib versus platinum-based chemotherapy

PFS 16.6 vs 8.1

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the rapid development and approval of other next generation ALK inhibitor has diluted the importance of this finding.

Soria JC, Tan DSW, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK -rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. The Lancet. 2017;389(10072):917-929. doi:10.1016/S0140-6736(17)30123-X

First-line ceritinib versus platinum-based chemotherapy

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OS

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Soria JC, Tan DSW, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK -rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. The Lancet. 2017;389(10072):917-929. doi:10.1016/S0140-6736(17)30123-X

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Lorlatinib

3rd generation ALKi

CROWN 👑

First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer

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  • Phase 3, Randomized

  • Multi-center, Open-label

  • Number of patients: 296

    • Advanced ALK-positive NSCLC
    • Received no previous systemic treatment for metastatic disease

:::split

Agent

  • Lorlatinib, 100 mg once daily
  • Crizotinib, 250mg BID

  1. Treatment line: First-line treatment for advanced ALK-positive NSCLC

  2. Trial Name or NCT Number: CROWN 👑 ClinicalTrials.gov number, NCT03052608 :::

Shaw AT, Bauer TM, de Marinis F, et al. First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. New England Journal of Medicine. 2020;383(21):2018-2029. doi:10.1056/NEJMoa2027187

  1. Comparison of two groups: | Endpoint | Lorlatinib | Crizotinib | | ----------------------------------------------------------------------- | --------------------------- | ---------------------- | | Progression-free survival at 12 months | 78% (95% CI, 70 to 84) | 39% (95% CI, 30 to 48) | | Hazard ratio for disease progression or death | 0.28 (95% CI, 0.19 to 0.41) | Not reported | | Objective response | 76% (95% CI, 68 to 83) | 58% (95% CI, 49 to 66) | | Intracranial response (among patients with measurable brain metastases) | 82% (95% CI, 57 to 96) | 23% (95% CI, 5 to 54) | | Intracranial complete response | 71% | Not reported |

Shaw AT, Bauer TM, de Marinis F, et al. First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. New England Journal of Medicine. 2020;383(21):2018-2029. doi:10.1056/NEJMoa2027187

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Shaw AT, Bauer TM, de Marinis F, et al. First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. New England Journal of Medicine. 2020;383(21):2018-2029. doi:10.1056/NEJMoa2027187

Cumulative Incidence of CNS Progression as First Event

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Shaw AT, Bauer TM, de Marinis F, et al. First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. New England Journal of Medicine. 2020;383(21):2018-2029. doi:10.1056/NEJMoa2027187

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Shaw AT, Bauer TM, de Marinis F, et al. First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. New England Journal of Medicine. 2020;383(21):2018-2029. doi:10.1056/NEJMoa2027187

Timeline in the development of the AEs of lorlatiib

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Ou SHI, Lee ATM, Nagasaka M. From preclinical efficacy to 2022 (36.7 months median follow -up) updated CROWN trial, lorlatinib is the preferred 1st-line treatment of advanced ALK+ NSCLC. Critical Reviews in Oncology/Hematology. 2023;187:104019. doi:10.1016/j.critrevonc.2023.104019 Bauer TM, Felip E, Solomon BJ, et al. Clinical Management of Adverse Events Associated with Lorlatinib. Oncologist. 2019;24(8):1103-1110. doi:10.1634/theoncologist.2018-0380

Compare Trials of ALKi

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Schematic total PFS comparison

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Ou SHI, Lee ATM, Nagasaka M. From preclinical efficacy to 2022 (36.7 months median follow -up) updated CROWN trial, lorlatinib is the preferred 1st-line treatment of advanced ALK+ NSCLC. Critical Reviews in Oncology/Hematology. 2023;187:104019. doi:10.1016/j.critrevonc.2023.104019

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ALK inhibitor versus chemotherapy, outcome: 1.1 Progression-free survival subgrouped by line of treatment

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ALK inhibitor versus chemotherapy, outcome: 1.16 Overall survival subgrouped by line of treatment

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Next-generation ALK inhibitor versus crizotinib, outcome: 2.1 Progressionfree survival subgrouped by type of ALK inhibitor

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Next-generation ALK inhibitor versus crizotinib, outcome: 2.3 Overall adverse events subgrouped by type of ALK inhibitor

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Resistance
of ALKi

Mechanisms of resistance of ALKi

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Dagogo-Jack I, Shaw AT. Crizotinib resistance: implications for therapeutic strategies. Ann Oncol. 2016;27(Suppl 3):iii42-iii50. doi:10.1093/annonc/mdw305

Impact of EML4-ALK Variant on Resistance Mechanisms and Clinical Outcomes in ALK-Positive Lung Cancer

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Lin JJ, Zhu VW, Yoda S, et al. Impact of EML4-ALK Variant on Resistance Mechanisms and Clinical Outcomes in ALK-Positive Lung Cancer. JCO. 2018;36(12):1199-1206. doi:10.1200/JCO.2017.76.2294

PFS by EML4-ALK v1 versus v3 detected by cDNA (CROWN, ALEX, ALTAl-1L)

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Ou SHI, Lee ATM, Nagasaka M. From preclinical efficacy to 2022 (36.7 months median follow -up) updated CROWN trial, lorlatinib is the preferred 1st-line treatment of advanced ALK+ NSCLC. Critical Reviews in Oncology/Hematology. 2023;187:104019. doi:10.1016/j.critrevonc.2023.104019

Secondary Mutations within EML4-ALK

EML4-ALK cDNA clones prepared from sputum specimens obtained from our patient before crizotinib treatment and from pleural-effusion specimens obtained after relapse. :::free Figure: height:350px :::split Figure: height:350px :::

Choi YL, Soda M, Yamashita Y, et al. EML4-ALK Mutations in Lung Cancer That Confer Resistance to ALK Inhibitors. New England Journal of Medicine. 2010;363(18):1734-1739. doi:10.1056/NEJMoa1007478 Lovly CM, Pao W. Escaping ALK Inhibition: Mechanisms of and Strategies to Overcome Resistance. Sci Transl Med. 2012;4(120). doi:10.1126/scitranslmed.3003728

Characteristics of the pooled population of 450 ALK inhibitor resistant

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Koopman B, Groen HJM, Schuuring E, et al. Actionability of on-target ALK Resistance Mutations in Patients With Non-Small Cell Lung Cancer: Local Experience and Review of the Literature. Clinical Lung Cancer. 2022;23(2):e104-e115. doi:10.1016/j.cllc.2021.06.011

Clinical Benefit for ALK Resistance Mutations From Sequential ALK Inhibitors

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Koopman B, Groen HJM, Schuuring E, et al. Actionability of on-target ALK Resistance Mutations in Patients With Non-Small Cell Lung Cancer: Local Experience and Review of the Literature. Clinical Lung Cancer. 2022;23(2):e104-e115. doi:10.1016/j.cllc.2021.06.011

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Recondo G, Facchinetti F, Olaussen KA, Besse B, Friboulet L. Making the first move in EGFR-driven or ALK-driven NSCLC: first-generation or next-generation TKI? Nat Rev Clin Oncol. 2018;15(11):694-708. doi:10.1038/s41571-018-0081-4

Take Home Message

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  • 健保 2023-11-01
    • Lorlatinib與alectinib、ceritinib、crizotinib、brigatinib用於ALK陽性之晚期非小細胞肺癌第一線治療時，僅得擇一使用
  • Lorlatinib: Excellent CNS activity
  • Lorlatinib AEs: hypercholesterolemia, hypertriglyceridemia, cognitive AEs, peripheral neuropathy, and edema
  • Resistance of ALKi: Variant 3 and G1202R :::split Figure: height:450px :::split Figure: height:500px :::

Singh N, Jaiyesimi IA, Ismaila N, et al. Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2023.1. JCO. 2023;41(15):e42-e50. doi:10.1200/JCO.23.00281

Thank you for your time and attention

Have a nice day

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Addendum

Adjuvant
ALK Inhibitor

ALCHEMIST: Bringing genomic discovery and targeted therapies to early-stage lung cancer

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ALINA: Randomized Phase III Trial of Adjuvant Alectinib vs Chemotherapy in Patients With Stage IB-IIIA ALK-Positive NSCLC

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Graph View

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