Clinical activity and tolerability of BLU-667, a highly potent and selective RET inhibitor, in patients (pts) with advanced RET-fusion+ non-small cell lung cancer (NSCLC).

Gainor, Justin F.; Lee, Dong Hoon; Curigliano, Giuseppe; Doebele, Robert C.; Kim, Dong-Wan; Baik, Christina S.; Tan, Daniel Shao-Weng; Lopes, Gilberto; Gadgeel, Shirish M.; Cassier, Philippe; Taylor, Matthew H.; Liu, Stephen V.; Besse, Benjamin; Thomas, Michael; Zhu, Viola W.; Zhang, Hui; Clifford, Corinne; Palmer, Michael C.; Turner, Christopher D.; Subbiah, Vivek

doi:10.1200/jco.2019.37.15_suppl.9008

Cited by 93 publications

(91 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, recent therapeutic targeting of these cancers has shifted to RET-specific inhibition. Recently, RET-specific inhibitors BLU-667 and LOXO-292 have been investigated and preliminary clinical data suggest that they may be effective anticancer agents in patients with NSCLC and other cancers harboring RET translocations [29][30][31][32]. Subbiah et al reported anticancer activity in 2 patients with KIF5B-RET fusions where both patients showed a PR after 16 weeks of treatment with BLU-667 at doses of 200-300 mg/d [29].…”

Section: Discussionmentioning

confidence: 99%

“…Subbiah et al reported anticancer activity in 2 patients with KIF5B-RET fusions where both patients showed a PR after 16 weeks of treatment with BLU-667 at doses of 200-300 mg/d [29]. In the ARROW study, BLU-667 demonstrated potent antitumor activity and was well tolerated in patients with RET fusion-positive NSCLC [32]. Of the 79 patients enrolled, 44 had KIF5B-RET and 16 had CCDC6-RET fusions.…”

Section: Discussionmentioning

confidence: 99%

“…Of the 79 patients enrolled, 44 had KIF5B-RET and 16 had CCDC6-RET fusions. The ORR was 56% (95% CI, 42-69; 32 PR, 9 PR pending confirmation, 20 SD, 5 PD) (NCT03037385) [32]. Additionally, in a phase 1 study of 26 patients with RET fusion-positive NSCLC treated with the RET-targeted inhibitor LOXO-292, the ORR was 65% (17/26) (NCT03157128) [30].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

A phase 2 study of lenvatinib in patients with RET fusion-positive lung adenocarcinoma

et al. 2019

View full text Add to dashboard Cite

Despite improved outcomes associated with immunotherapies for non-small cell lung cancer (NSCLC), many patients do not respond to treatment. Therefore, there is still an unmet need for molecularly targeted therapies in this patient population. Fusions of the RET oncogene have been identified as driver alterations in patients with NSCLC. Lenvatinib is a multityrosine kinase inhibitor of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, RET, and other targets. This study evaluated the safety and efficacy of lenvatinib in patients with RET fusion-positive lung adenocarcinoma. Materials and methods: In this phase 2, multicenter, open-label study (NCT01877083), patients with RET-positive lung adenocarcinoma received oral lenvatinib 24 mg/day. The primary end point was objective response rate (ORR) by investigator review per Response Evaluation Criteria In Solid Tumors v1.1 criteria. The secondary end points included safety and tolerability, progression-free survival (PFS), and overall survival (OS). Results: Of 536 patients who screened for study inclusion and exclusion, 25 patients with RET translocations (KIF5B-RET [n = 13] and CCDC6-RET [n = 12]) were identified and received lenvatinib. The overall ORR was 16% (95% CI: 4.5%-36.1%). At data cutoff (February 3, 2016), the median PFS was 7.3 months (95% CI: 3.6-10.2) and the median OS was not reached. Duration of response was not estimable at the time of data cutoff. All patients experienced a treatment-emergent adverse event (TEAE); 23 (92%) patients experienced a TEAE of ≥ grade 3, and 6 (24%) patients discontinued lenvatinib due to a TEAE. The most common TEAEs were hypertension (68%), nausea (60%), decreased appetite (52%), diarrhea (52%), and proteinuria (48%). Conclusions: Lenvatinib demonstrated activity in patients with RET fusion-positive lung adenocarcinomas; although the response rate was relatively low, the median PFS supports the activity of lenvatinib in these patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A phase 2 study of lenvatinib in patients with RET fusion-positive lung adenocarcinoma

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Gainor et al presented preliminary efficacy data with the RET inhibitor BLU-667 [7]. BLU-667 was explored in a dose-escalation study that resulted in a maximum tolerated dose of 400 mg per day.…”

Section: Ret-fusion: Selective Ret Inhibitors Show Durable Responsesmentioning

confidence: 99%

“…Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations 7. For latest news from international oncology congresses see: http://www.springermedizin.at/ memo-inoncology…”

mentioning

confidence: 99%

Targeted therapy in lung cancer—ASCO 2019 update

Wass

Lang

Lamprecht

et al. 2019

memo

View full text Add to dashboard Cite

New targeted therapies for patients with non small cell lung cancer were presented at this year's ASCO. EGFR exon 20 insertions might soon be treatable with TAK-788, which showed an objective response rate (ORR) of between 25 and 56% with a disease control rate (DCR) between 67 and 100% depending on the presence or absence of brain metastases at baseline. Capmatinib and tepotinib showed durable responses in MET exon 14 mutations as presented in the phase II GEOMETRY trial and the VISION trial. The median duration of response (DOR) was 9.7 months with a median progression free survival (PFS) of 5.42 months in pretreated patients and 11.14 months respective 9.6 months in those receiving capmatinib in the frontline setting. Tepotinib showed similar results with a median DOR of 12.4 months and a DCR of 66.7%. For RET-fusion lung cancer the well tolerated RET inhibitor BLU-667 has already been granted breakthrough therapy designation. Among previously treated patients an ORR of 58% and a DCR

show abstract

Real‐world utility of next‐generation sequencing for targeted gene analysis and its application to treatment in lung adenocarcinoma

et al. 2021

Self Cite

View full text Add to dashboard Cite

Purpose This study investigated the clinical utility of next‐generation sequencing (NGS) for detection of genetic alterations and its implications on treatment of lung adenocarcinoma in real‐world practice. Patients and Methods Data were reviewed for 391 patients with lung adenocarcinoma who underwent NGS between March 2017 and October 2018. Formalin‐fixed, paraffin‐embedded archival samples were used for performing NGS targeting 382 genes, including all exons of 199 genes, 184 hotspots, and the partial introns of 8 genes often rearranged in cancer. Survival analysis was performed for stage IV disease. Results Among the 391 patients, at least one actionable mutation was identified in 294 patients (75.2%). The most commonly mutated gene was EGFR (n = 130, 33.2%), involving EGFR exon 19 deletion (n = 48, 12.3%), L858R (n = 47, 12%), and others (n = 35, 9%), followed by KRAS (n = 48, 12.3%), ALK (n = 40, 10.2%), RET (6%), MET (3%), ROS‐1 (3%), and BRAF (2%) mutations. TP53 (46.9%) and CDKN2A (12.6%) mutations were common co‐mutations in patients with AMs. With a median follow‐up duration of 16.8 months, median overall survival was 36.8 months in patients with stage IV disease. Patients treated with the corresponding targeted therapy for AMs based on NGS reports lived significantly longer than those not treated with such therapy (p < 0.001). After multivariate analysis, targeted therapy for AM was a significantly favorable factor for survival (AM without targeted therapy vs. AM with targeted therapy, hazard ratio 2.58, 95% confidence interval 1.57–4.25; p < 0.001). Conclusion This study revealed that AMs could be comparably detected using NGS. Based on these NGS results, a suitable targeted therapy can be selected, which may improve survival in patients with lung adenocarcinoma. This NGS‐based approach is useful in real‐world practice to provide guidance when selecting targeted therapy.

show abstract

Clinical activity and tolerability of BLU-667, a highly potent and selective RET inhibitor, in patients (pts) with advanced RET-fusion+ non-small cell lung cancer (NSCLC).

Cited by 93 publications

References 0 publications

A phase 2 study of lenvatinib in patients with RET fusion-positive lung adenocarcinoma

A phase 2 study of lenvatinib in patients with RET fusion-positive lung adenocarcinoma

Targeted therapy in lung cancer—ASCO 2019 update

Real‐world utility of next‐generation sequencing for targeted gene analysis and its application to treatment in lung adenocarcinoma

Contact Info

Product

Resources

About