Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study

Solomon, Benjamin; Besse, Benjamin; Bauer, Todd M.; Felip, Enriqueta; Soo, Ross A.; Camidge, D. Ross; Chiari, Rita; Bearz, Alessandra; Lin, Chia Chi; Gadgeel, Shirish M.; Riely, Gregory J.; Tan, Eng Huat; Seto, Takashi; James, Leonard P.; Clancy, Jill S.; Abbattista, Antonello; Martini, Jean-François; Chen, Joseph; Peltz, Gerson; Thurm, Holger; Ou, Sai Hong Ignatius; Shaw, Alice T.

doi:10.1016/s1470-2045(18)30649-1

Cited by 651 publications

(637 citation statements)

References 26 publications

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“…In addition, as a first‐line treatment for ALK (+) NSCLC, ceritinib significantly improved PFS compared with platinum doublet chemotherapy . In September 2018, the use of lorlatinib, a third‐generation ALK‐TKI, which had better potency to secondary resistance mutation than that of prior generation ALK‐TKI in a preclinical model, was approved for the treatment of patients whose disease has progressed after crizotinib failure or those who had been treated with another ALK‐TKI based on the promising results of a phase I/II trial investigating the efficacy of such drugs in patients with ALK (+) lung cancer …”

Section: Introductionmentioning

confidence: 99%

“…10 In September 2018, the use of lorlatinib, a third-generation ALK-TKI, which had better potency to secondary resistance mutation than that of prior generation ALK-TKI in a preclinical model, 11 was approved for the treatment of patients whose disease has progressed after crizotinib failure or those who had been treated with another ALK-TKI based on the promising results of a phase I/II trial investigating the efficacy of such drugs in patients with ALK (+) lung cancer. 12,13 Due to these developments, several ALK-TKI are used sequentially in clinical practice at present. 14 However, disease progression due to acquired resistance inevitably occurs after several years, resulting in a major problem in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

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Drug resistance mechanisms in Japanese anaplastic lymphoma kinase‐positive non–small cell lung cancer and the clinical responses based on the resistant mechanisms

et al. 2020

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The treatment for anaplastic lymphoma kinase (ALK)‐positive lung cancer has been rapidly evolving since the introduction of several ALK tyrosine kinase inhibitors (ALK‐TKI) in clinical practice. However, the acquired resistance to these drugs has become an important issue. In this study, we collected a total of 112 serial biopsy samples from 32 patients with ALK‐positive lung cancer during multiple ALK‐TKI treatments to reveal the resistance mechanisms to ALK‐TKI. Among 32 patients, 24 patients received more than two ALK‐TKI. Secondary mutations were observed in 8 of 12 specimens after crizotinib failure (G1202R, G1269A, I1171T, L1196M, C1156Y and F1245V). After alectinib failure, G1202R and I1171N mutations were detected in 7 of 15 specimens. G1202R, F1174V and G1202R, and P‐gp overexpression were observed in 3 of 7 samples after ceritinib treatment. L1196M + G1202R, a compound mutation, was detected in 1 specimen after lorlatinib treatment. ALK‐TKI treatment duration was longer in the on‐target treatment group than that in the off‐target group (13.0 vs 1.2 months). In conclusion, resistance to ALK‐TKI based on secondary mutation in this study was similar to that in previous reports, except for crizotinib resistance. Understanding the appropriate treatment matching resistance mechanisms contributes to the efficacy of multiple ALK‐TKI treatment strategies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Drug resistance mechanisms in Japanese anaplastic lymphoma kinase‐positive non–small cell lung cancer and the clinical responses based on the resistant mechanisms

et al. 2020

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“…One of the main contributions to this poor prognosis in the high rate of metastasis for canine HSA; thus, systemic therapy targeting the metastatic lesions as well as the original tumour should be developed. Recently, many new concept small‐molecule compounds such as tyrosine kinase inhibitors or anti‐tumour cytokines have been applied to treatment of systemic cancers in both human and veterinary medicine …”

Section: Introductionmentioning

confidence: 99%

“…Recently, many new concept small-molecule compounds such as tyrosine kinase inhibitors or anti-tumour cytokines have been applied to treatment of systemic cancers in both human and veterinary medicine. [13][14][15][16][17] One such promising molecule is tumour necrosis factor (TNF)related apoptosis-inducing ligand (TRAIL), also called Apo2 ligand (Apo2L), which is a representative anti-tumour cytokine belonging to the TNF protein family. 18,19 TRAIL is transcribed in many normal tissues, including the spleen, thymus, prostate, lung and tonsillar Tcells, as well as in several lymphoma cells such as Raji and K299 cells.…”

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confidence: 99%

Tumour necrosis factor‐related apoptosis‐inducing ligand induces apoptosis in canine hemangiosarcoma cells in vitro

Goto

Owaki

Hirata

et al. 2019

Vet Comparative Oncology

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Tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL) is an apoptosis‐inducing cytokine that shows potential therapeutic value for human neoplasms, and is effective in some canine tumours; however, its potential for killing canine hemangiosarcoma (HSA) cells is unknown. Thus, we evaluated the proapoptotic effect of TRAIL in nine canine HSA cell lines. Cells (JuA1, JuB2, JuB2‐1, JuB4, Re11, Re12, Re21, Ud2 and Ud6) were cultured with three recombinant human TRAILs (rhTRAILs): TRAIL‐TEC derived from Escherichia coli, TRAIL‐TL derived from mammalian cells and isoleucine zipper recombinant human TRAIL (izTRAIL) containing an isoleucine‐zippered structure that facilitates trimerization. TRAIL‐TEC did not decrease the cell viability in any of the cell lines tested, whereas the other two rhTRAILs effectively decreased the viability of all cell lines as assessed by the WST‐1 assay. In canine HSA cells, izTRAIL induced apoptosis more effectively than TRAIL‐TL. In JuB4, Re12, and Ud6 cells, izTRAIL increased the activation of caspase‐3 and caspase‐8 and caused poly (ADP‐ribose) polymerase degradation. Moreover, izTRAIL treatment increased the proportion of Annexin V+/ Propidium iodide (PI)− apoptotic cells and nuclear fragmentation in izTRAIL‐sensitive cells. These results show that rhTRAIL can induce apoptosis in canine HSA cells, but the sensitivity of TRAIL was different depending on the cell lines. Therefore, TRAIL could be an effective therapeutic agent against canine HSA, but the specific mechanism of resistance should be determined to clarify under what conditions this treatment would be most effective.

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“…Crizotinib altında progresyon gösteren hastalarda ise benzer şekilde alektinib, ceritinib, brigatinib ve lorlatinib kemoterapiye karşı etkinlikleri gösterilmiş ajanlardır. (12)(13)(14)(15) Birinci basamakta crizotnibin araştırıldığı PROFILE 1014 çalışmasının güncellenmiş genel sağkalım verilerinde crizotinib ile medyan sağkalıma ulaşılamamışken kemoterapi ile 47,50 ay…”

Section: Introductionunclassified

Clinical Feature and Survival Outcomes of Lung Cancer with ALK Mutation Positive and Treated with Crizotinib, Single Centre Experience

Bi̇lgi̇n¹,

Yücel²

2019

Acta Oncol Tur.

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ÖZET GİRİŞ ve AMAÇ: ALK pozitif akciğer kanseri tüm akciğer kanserli olguları küçük bir bölümünü oluşturur. Özellikle son yıllarda ALK mutasyonu pozitif olgularda hedefe yönelik tedavilerin geliştirilmesi ile sağkalım sonuçlarında belirgin iyileşmeler görülmektedir. Bu çalışmada da ALK mutasyonu pozitif ve herhangi bir basamakta crizotinib uygulanmış akciğer kanserli olgularda klinik özelliklerin ve sağkalım sonuçlarının belirlenmesi amaçlanmıştır. YÖNTEM ve GEREÇLER: Ankara Atatürk Göğüs Hastalıkları ve Göğüs Cerrahisi Eğitim ve Araştırma Hastanesi, Tıbbi onkoloji polikliniğine 2014 -2018 yılları arasında başvurmuş hastalar çalışmaya dahil edilmiş ve verileri retrospektif olarak toplanmıştır. BULGULAR: Toplam 48 hasta çalışmaya dahil edilmiş olup hastaların büyük çoğunluğu metastatik (%86,7) ve sigara içmemiş (%68,8) hastalardan oluşmaktaydı. Birinci basamakta crizotinib kullanan hastalarda crizotinib ile elde edilen progresyonsuz sağkalım medyan 13,04 ay olarak saptandı. Daha önce bir basamak kemoterapi alan hastalarda ise crizotinib ile PS 16,88 ay olarak bulundu. Tüm grup ele alındığında metastatik olma zamanından itibaren genel sağkalım 37,74 ay olarak saptanmıştır TARTIŞMA ve SONUÇ: ALK mutasyonu pozitif akciğer kanseri olgularında sağkalım süresi kemoterapi ile karşılaştırıldığında hedefe yönelik tedaviler ile belirgin olarak artmıştır. Bizim çalışmamızda da crizotinib ile tek merkez gerçek yaşam verileri ikinci basamak hariç literatürle uyumludur. Anahtar Kelimeler: Crizotinib, ALK mutasyonu, Akciğer kanseri ABSTRACT INTRODUCTION: Non-small cell lung cancer (NSCLC) with ALK-mutation is a small group of lung cancer. Especially last years, treatment outcomes of NSCLC with ALK-mutation are increased due to developing many new targeted therapies against ALK mutation. In this study, we aim to detect clinical feature and survival outcomes of patients who had ALK mutation positive and treated with crizotinib in any treatment line. METHODS: The patients who followed in Ankara Atatürk Chest Disease and Chest Surgery Education and Research Hospital, Department of Medical Oncology between 2014-2018 were enrolled. The data of patients were obtained retrospectively. RESULTS: Totally, 48 patients were enrolled to study and most of these patients were metastatic (86.7%) and non-smoker (68.8%). Median progression-free survival (PFS) of the patients who treated with crizotinib as firstline and second-line (after one-line chemotherapy) were 13.04 months and 16.88 months, respectively. Overall survival of patients who treated with crizotinib in any treatment-line was 37.74 months. DISCUSSION AND CONCLUSION:In NSCLC with ALK-mutation, superior outcomes are obtained with crizotinib and the other tyrosine kinase inhibitors that targeted to ALK. In our study, real-life data of crizotinib was found as compatible with the previous trial except for second-line treatment

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Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study

Cited by 651 publications

References 26 publications

Drug resistance mechanisms in Japanese anaplastic lymphoma kinase‐positive non–small cell lung cancer and the clinical responses based on the resistant mechanisms

Drug resistance mechanisms in Japanese anaplastic lymphoma kinase‐positive non–small cell lung cancer and the clinical responses based on the resistant mechanisms

Tumour necrosis factor‐related apoptosis‐inducing ligand induces apoptosis in canine hemangiosarcoma cells in vitro

Clinical Feature and Survival Outcomes of Lung Cancer with ALK Mutation Positive and Treated with Crizotinib, Single Centre Experience

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