Efficacy of Selpercatinib in <i>RET</i> Fusion–Positive Non–Small-Cell Lung Cancer

Drilon, Alexander; Oxnard, Geoffrey R.; Tan, Daniel Shao-Weng; Loong, Herbert H.; Johnson, Melissa L.; Gainor, Justin F.; McCoach, Caroline E.; Gautschi, Oliver; Besse, Benjamin; Cho, Byoung Chul; Peled, Nir; Weiss, Jared; Kim, Yu-Jung; Ohe, Yuichiro; Nishio, Makoto; Park, Keunchil; Patel, Jyoti D.; Seto, Takashi; Sakamoto, Tomohiro; Rosen, Ezra Y.; Shah, Manisha H.; Barlési, Fabrice; Cassier, Philippe; Bazhenova, Lyudmila; Braud, Filippo de; Garralda, Elena; Velcheti, Vamsidhar; Satouchi, Miyako; Ohashi, Kadoaki; Pennell, Nathan A.; Reckamp, Karen L.; Dy, Grace K.; Wolf, Jürgen; Solomon, Benjamin; Falchook, Gerald S.; Ebata, Kevin; Nguyen, M.; Nair, Binoj C.; Zhu, Edward Y.; Yang, Luxi; Huang, Xin; Olek, Elizabeth; Rothenberg, S. Michael; Goto, Kōichi; Subbiah, Vivek

doi:10.1056/nejmoa2005653

Cited by 617 publications

(556 citation statements)

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“…The single-arm trial, LIBRETTO-001 reported the outcomes of 105 patients with RET-fusion positive NSCLC. In this study, one patient had squamous cell carcinoma [ 18 ]. The current study supports the rarity of RET fusions in squamous NSCLC.…”

Section: Discussionmentioning

confidence: 99%

“…Selpercatinib was approved for use in the U.S. in May 2020 for patients with RET -fusion positive non-small cell lung cancer, RET -fusion positive thyroid cancer, or RET -mutation positive meduallary thyroid cancer. This approval was based on a single-arm phase I/II trial, LIBRETTO-001, which demonstrated overall tumor response rates of 85 and 64% for patients with RET-fusion positive NSCLC who were treatment naïve and previously treated, respectively [ 17 , 18 ]. Response rates were similar for patients with RET altered thyroid (treatment naïve, 100%; previously treated, 79%) and medullary thyroid cancers (no prior multikinase inhibitors [MKIs], 73%, previously treated with MKIs, 69%) [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Characteristics and outcomes of patients with RET-fusion positive non-small lung cancer in real-world practice in the United States

et al. 2021

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Background Contradictory and limited data are available about the presentation and outcomes of patients with RET-fusion positive metastatic NSCLC as compared to patients without RET fusions. This observational study utilizing a linked electronic health records (EHR) database to genomics testing results was designed to compare characteristics, tumor response, progression-free (PFS) and overall survival (OS) outcomes by RET fusion status among patients with metastatic NSCLC treated with standard therapies. Methods Adult patients with metastatic NSCLC with linked EHR and genomics data were eligible who received systemic anti-cancer therapy on or after January 1, 2011. Adjusted, using all available baseline covariates, and unadjusted analyses were conducted to compare tumor response, PFS and OS between patients with RET-fusion positive and RET-fusion negative disease as detected by next-generation sequencing. Tumor response outcomes were analysed using Fisher’s exact test, and time-to-event analyses were conducted using Cox proportional hazards model. Results There were 5807 eligible patients identified (RET+ cohort, N = 46; RET- cohort, N = 5761). Patients with RET fusions were younger, more likely to have non-squamous disease and be non-smokers and had better performance status (all p < 0.01). In unadjusted analyses, there were no significant differences in tumor response (p = 0.17) or PFS (p = 0.06) but OS was significantly different by RET status (hazard ratio, HR = 1.91, 95% CI:1.22–3.0, p = 0.005). There were no statistically significant differences by RET fusion status in adjusted analyses of either PFS or OS (PFS HR = 1.24, 95% CI:0.86–1.78, p = 0.25; OS HR = 1.52, 95% CI: 0.95–2.43, p = 0.08). Conclusions Patients with RET fusions have different baseline characteristics that contribute to favorable OS in unadjusted analysis. However, after adjusting for baseline covariates, there were no significant differences in either OS or PFS by RET status among patients treated with standard therapy prior to the availability of selective RET inhibitors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characteristics and outcomes of patients with RET-fusion positive non-small lung cancer in real-world practice in the United States

et al. 2021

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“…Moreover, Kurzrock summarises the impressive data reported by Drilon et al in the cohort of patients with RET fusionpositive NSCLC both naïve or previously exposed to platinum achieving durable efficacy with intracranial activity and a favourable safety profile. 8 In conclusion, selpercatinib has shown great efficacy with long-lasting responses together with scarce toxicity in patients with RET-altered medullary thyroid cancer or NSCLC, both naïve and pretreated. However, perhaps the main take-home message is the need to incorporate the detection of RET alterations into the routine molecular diagnostic panel for thyroid and NSCLC.…”

Section: Ret-altered Thyroid Cancers: a New Paradigm For Targeted Thementioning

confidence: 90%

In the literature: October 2020

2020

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“…Importantly, an objective intracranial response was noted in patients with measurable central nervous system (CNS) metastasis, which was consistent with the efficient brain penetration of selpercatinib. 4 …”

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confidence: 99%

“…Overall, 30% of patients required a dose reduction because of treatment-related adverse events, and 2% discontinued selpercatinib because of treatment-related adverse events. 3 , 4 , 5 …”

mentioning

confidence: 99%