Αρχική World News Selpercatinib Shows Durable Efficacy in RET Fusion–positive NSCLC

Selpercatinib Shows Durable Efficacy in RET Fusion–positive NSCLC

RET fusions are oncogenic drivers in 1% to 2% of patients with non-small cell lung cancer (NSCLC). The LIBRETTO-001 study investigators reported on 27 August 2020 in The New England Journal of Medicine that among patients with RET fusion-positive NSCLC who were previously treated with at least platinum-based chemotherapy, treatment with a RET kinase inhibitor, selpercatinib, resulted in 64% objective response. Furthermore, 85% of previously untreated patients with NSCLC achieved objective response with selpercatinib. The percentage of an objective intracranial response with selpercatinib was 91%. Adverse events of grade 3 or higher were reported in approximately one third of patients.

The authors reported that activating RET fusions typically occur in a mutually exclusive fashion with other oncogenic drivers. RET fusions appear to be associated with a high risk of brain metastases. Multitargeted kinase inhibitors that have some measure of RET inhibition result in only limited clinical benefit with toxic effects that lead to frequent dose reductions or permanent drug discontinuation.

Selpercatinib is a novel, ATP-competitive, highly selective small-molecule inhibitor of RET kinase. Selpercatinib was designed to penetrate the central nervous system (CNS). Its efficacy was evaluated in an open-label phase I/II LIBRETTO-001 trial. Adolescent and adult patients with any type of solid tumour harbouring an activating RET alteration (e.g. fusions or mutations) were eligible for inclusion.

A cohort of patients with advanced RET fusion–positive NSCLC consists of the patients who had previously received platinum-based chemotherapy and those who were previously untreated. The primary study endpoint was an objective response (a complete or partial response) as determined by an independent review committee. Secondary endpoints included the duration of response, progression-free survival, and safety.

In the first 105 enrolled patients with RET fusion–positive NSCLC (49 included in the phase I dose-escalation portion of the trial and 56 patients included in the phase I dose-expansion or phase II portion of the trial), from whom all were previously treated with at least platinum-based chemotherapy, the percentage of the objective response was 64% (95% confidence interval [CI], 54 to 73). The median duration of response was 17.5 months (95% CI, 12.0 to could not be evaluated) and 63% of the responses were ongoing at a median follow-up of 12.1 months.

Among 39 previously untreated NSCLC patients, the objective response was 85% (95% CI, 70 to 94), and 90% of the responses were ongoing at 6 months.

Among 11 patients with measurable CNS metastasis at study enrolment, the objective intracranial response was 91% (95% CI, 59 to 100).

The study team reported that most common adverse events of grade 3 or higher were hypertension in 14% of the patients, an increased alanine aminotransferase in 12%, an increased aspartate aminotransferase in 10%, hyponatremia in 6% and lymphopenia in 6%. Six grade 5 adverse events were observed, but they were determined by the study investigators as being unrelated to selpercatinib. Dose reduction was warranted in 30% of patients because of treatment-related adverse events. In total, 2% discontinued selpercatinib because of treatment-related adverse events, the most common of which were an increase in the alanine aminotransferase in 2 patients and drug hypersensitivity in 2 patients.

The authors concluded that selpercatinib has substantial antitumour activity in patients with RET fusion–positive NSCLC. Antitumor activity was observed regardless of previous exposure to anti–PD-1 or anti–PD-L1 therapy or multikinase inhibitors. The authors underlined that implementation of molecular screening strategies that include detection of RET fusions will be critical for identifying patients with NSCLC who may benefit from the treatment with selpercatinib.

Razelle Kurzrock of the Moores Cancer Center, University of California in San Diego, CA, US, who commented the study findings, wrote in an accompanied editorial that selpercatinib showed in the LIBRETTO-001 study marked and durable antitumour activity in most patients with RET-altered thyroid cancer and NSCLC. RET abnormalities now join the genomic alterations such as NTRK fusions, tumour mutation burden, and deficient mismatch-repair genes across cancers and ALK, BRAF, EGFR, MET, and ROS1 alterations in NSCLC that warrant molecular screening strategies. 

The LIBRETTO-001 study was supported by Loxo Oncology, a wholly owned subsidiary of Eli Lilly, and by grants from the US National Institutes of Health and the University of Texas M.D. Anderson Cancer Center.





Συμπληρώστε το email σας για να λαμβάνετε τις σημαντικότερες ειδήσεις από το ogkologos.com

Βρείτε μας

2,449ΥποστηρικτέςΚάντε Like

Διαβαστε Επίσης


ΕΞΕΛΙΞΕΙΣ ΣΤΗ ΘΕΡΑΠΕΙΑ ΤΟΥ ΜΗ-ΜΙΚΡΟΚΥΤΤΑΡΙΚΟΥ ΚΑΡΚΙΝΟΥ ΤΟΥ ΠΝΕΥΜΟΝΑ (ΜΜΚΠ) Γράφει ο Δρ Παπαδούρης Σάββας, Παθόλογος-Ογκολόγος   Ο ΜΜΚΠ βρίσκεται αναλογικά στο 80% και πλέον του συνολικού...

Διατρέχουν όντως οι καρκινοπαθείς μεγαλύτερο κίνδυνο λόγω κοροναϊού;

Σε πρακτικό επίπεδο, τα δεδομένα των σχετικών μελετών υποδηλώνουν ότι η χημειοθεραπεία ή οι άλλες αντι-νεοπλασματικές θεραπείες δεν αυξάνουν σημαντικά τον κίνδυνο θνησιμότητας από...

FDA: Η ακτινοβολία των smartphones δεν προκαλεί καρκίνο

Σε μια νέα έκθεσή της, η Υπηρεσία Τροφίμων και Φαρμάκων (FDA) των ΗΠΑ αναφέρει ότι επανεξέτασε τις σχετικές επιστημονικές έρευνες που δημοσιεύθηκαν τα τελευταία...

Νέα ανακάλυψη, νέα ελπίδα για τον καρκίνο

Ένα νεοανακαλυφθέν τμήμα του ανοσοποιητικού μας συστήματος θα μπορούσε να αξιοποιηθεί για την αντιμετώπιση όλων των ειδών καρκίνου, σύμφωνα με επιστήμονες του πανεπιστημίου Cardiff...

Καρκίνος: Ευεργετική για τους καρκινοπαθείς η άσκηση

Σημαντικά ωφέλη προσφέρει η άσκηση, ακόμη και σε ασθενείς με καρκίνο. Οι περισσότεροι ασθενείς αγνοούν τα οφέλη που μπορεί να έχει γι’ αυτούς η συχνή...

Prostate Cancer

The article is provided by Scientific Communications Officer of NIPD Genetics, Ms Marina Charitou (MSc) Prostate Cancer Awareness Prostate cancer is the second most common cancer...
- Advertisment -

Ροή Ειδήσεων

An existing blood test for ovarian cancer has been re-evaluated. The results are in.

Ovarian cancer is the sixth most common cancer in women in the UK, with about 7,400 new cases every year. This number equates to...

How to Stay Healthy After Cancer

I try to pack helpful advice into every follow-up visit I have with patients, focusing on little tips that help foster healthy lifestyles. This...

Feasibility and Preliminary Efficacy Results of the Beat AML Study

Precision medicine in acute myeloid leukaemia (AML) is feasible in terms of providing cytogenetic and mutational data within 7 days, allowing their rapid incorporation into...

Woman Battles Breast Cancer While Pregnant, Delivers Healthy Baby Boy

When she was six months pregnant, Desiree Doughty noticed that something seemed to be wrong with her breasts. “I noticed that one of my breasts...

Pumpkin Season!

Halloween may look different this year but we can still decorate our homes and enjoy a favorite fall treat – pumpkin and pumpkin seeds....

ACHIEVE-2 Results of Oxaliplatin-Based Adjuvant Chemotherapy in Asian Patients with High-Risk Stage II Colon Cancer

The Asian researchers reported on 25 October 2020 in the Annals of Oncology that 3-month of combination therapy for adjuvant treatment of high-risk stage...