Lorlatinib Versus Pemetrexed-Based Chemotherapy in Patients With ALK-rearranged NSCLC Previously Treated With Alectinib

Takeyasu, Yuki; Yoshida, Tatsuya; Masuda, Ken; Shinno, Yuki; Okuma, Yusuke; Goto, Yasushi; Horinouchi, Hidehito; Yamamoto, Noboru; Ohe, Yuichiro

doi:10.1016/j.jtocrr.2022.100311

Cited by 3 publications

(13 citation statements)

References 16 publications

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“…In this observational study, we found the efficacy of lorlatinib to be comparable with previous reports of lorlatinib given after 1L alectinib in patients with ALK + NSCLC in clinical practice in Japan and globally. 12 , 13 The efficacy observed in patients treated with lorlatinib with or without brain metastases at lorlatinib initiation was similar to previous reports, 12 , 13 and no new brain metastases were reported throughout treatment in this follow-up period.…”

Section: Discussionsupporting

confidence: 88%

“… 15 At lorlatinib initiation, brain metastases were present in 49.0% of patients with any-line treatment, which was slightly lower than the previous single-institution study. 13 The current study included 49.0% of patients who had never smoked, which is similar to the previous report with 56% of patients being never smokers in the lorlatinib group. 13 A higher proportion (16.0%) of patients in the current study had an ECOG PS greater than or equal to 2 compared with none in the phase 2 study, which was a major difference and gives this study more generalizability to a larger patient population and increases its validity.…”

Section: Discussionsupporting

confidence: 82%

“… 13 The current study included 49.0% of patients who had never smoked, which is similar to the previous report with 56% of patients being never smokers in the lorlatinib group. 13 A higher proportion (16.0%) of patients in the current study had an ECOG PS greater than or equal to 2 compared with none in the phase 2 study, which was a major difference and gives this study more generalizability to a larger patient population and increases its validity. 5 The only difference in patient characteristics between 2L and ≥3L was an inversion of the male to female ratio.…”

Section: Discussionsupporting

confidence: 82%

“… 1 In a retrospective study, lorlatinib was found to be efficacious after failure of alectinib in patients with ALK + NSCLC. 13 To date, this was the only evidence in actual clinical practice of lorlatinib after 1L alectinib in Japan; however, this was at a single institution.…”

Section: Introductionmentioning

confidence: 89%

“… 5 , 11 There is evidence that reveals that lorlatinib has an impact on brain metastases, and there are favorable efficacy data in previous clinical trials. 1 , 12 , 13 …”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

A Retrospective, Multicenter, Observational Study to Evaluate Clinical Outcomes of Lorlatinib After Alectinib in Patients With ALK-Positive NSCLC in Japan

Goto¹,

Kenmotsu²,

Tamiya³

et al. 2023

JTO Clinical and Research Reports

Self Cite

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 89%

“… 5 , 11 There is evidence that reveals that lorlatinib has an impact on brain metastases, and there are favorable efficacy data in previous clinical trials. 1 , 12 , 13 …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A Retrospective, Multicenter, Observational Study to Evaluate Clinical Outcomes of Lorlatinib After Alectinib in Patients With ALK-Positive NSCLC in Japan

Goto¹,

Kenmotsu²,

Tamiya³

et al. 2023

JTO Clinical and Research Reports

Self Cite

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Treatment of advanced ALK-rearranged NSCLC following second-generation ALK–TKI failure

Fukuda,

Yoshida

2023

Expert Review of Anticancer Therapy

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From Development to Place in Therapy of Lorlatinib for the Treatment of ALK and ROS1 Rearranged Non-Small Cell Lung Cancer (NSCLC)

Fabbri,

Di Federico,

Astore

et al. 2023

Diagnostics

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Following the results of the CROWN phase III trial, the third-generation macrocyclic ALK inhibitor lorlatinib has been introduced as a salvage option after the failure of a first-line TKI in ALK-rearranged NSCLC, while its precise role in the therapeutic algorithm of ROS1 positive disease is still to be completely defined. The ability to overcome acquired resistance to prior generation TKIs (alectinib, brigatinib, ceritinib, and crizotinib) and the high intracranial activity in brain metastatic disease thanks to increased blood–brain barrier penetration are the reasons for the growing popularity and interest in this molecule. Nevertheless, the major vulnerability of this drug resides in a peculiar profile of related collateral events, with neurological impairment being the most conflicting and debated clinical issue. The cognitive safety concern, the susceptibility to heterogeneous resistance pathways, and the absence of a valid alternative in the second line are strongly jeopardizing a potential paradigm shift in this oncogene-addicted disease. So, when prescribing lorlatinib, clinicians must face two diametrically opposed characteristics: a great therapeutic potential without the intrinsic limitations of its precursor TKIs, a cytotoxic activity threatened by suboptimal tolerability, and the unavoidable onset of resistance mechanisms we cannot properly manage yet. In this paper, we give a critical point of view on the stepwise introduction of this promising drug into clinical practice, starting from its innovative molecular and biochemical properties to intriguing future developments, without forgetting its weaknesses.

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Lorlatinib Versus Pemetrexed-Based Chemotherapy in Patients With ALK-rearranged NSCLC Previously Treated With Alectinib

Cited by 3 publications

References 16 publications

A Retrospective, Multicenter, Observational Study to Evaluate Clinical Outcomes of Lorlatinib After Alectinib in Patients With ALK-Positive NSCLC in Japan

A Retrospective, Multicenter, Observational Study to Evaluate Clinical Outcomes of Lorlatinib After Alectinib in Patients With ALK-Positive NSCLC in Japan

Treatment of advanced ALK-rearranged NSCLC following second-generation ALK–TKI failure

From Development to Place in Therapy of Lorlatinib for the Treatment of ALK and ROS1 Rearranged Non-Small Cell Lung Cancer (NSCLC)

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