Αρχική World News Tipifarnib Demonstrates Encouraging Efficacy in Patients with Recurrent and/or Metastatic HNSCC with...

Tipifarnib Demonstrates Encouraging Efficacy in Patients with Recurrent and/or Metastatic HNSCC with HRAS Mutations

In a phase II study conducted in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) with mutant HRAS variant allele frequency ≥20%, treatment with tipifarnib produced an objective response rate (ORR) of 55%, median progression-free survival (PFS) of 5.6 months and a median overall survival (OS) of 15.4 months. The safety profile of tipifarnib was tolerable and manageable. The study findings are published by Dr Alan L. Ho of the Memorial Sloan Kettering Cancer Center in New York, NY, US and colleagues on 20 April 2021 in the Journal of Clinical Oncology.

The authors wrote in the background that since the approval of the anti-epidermal growth factor antibody cetuximab more than a decade ago, development of targeted therapies in HNSCC has been stymied by the limited number of druggable targets and the aggressiveness of drug-refractory disease.

Phase II and III clinical studies failed to show significant efficacy of farnesyltransferase inhibitors in tumour types predicted to be enriched for NRAS and KRAS mutations, ending the development as a pan–RAS-targeted strategy.

In HNSCC patient–derived xenograft models, farnesyltransferase inhibitor therapy induced regressions only in HRAS mutant models. In HNSCC, HRAS is a driver oncogenic mutation that occurs in approximately 4-8% of patients and defines a predominantly HPV-negative biologic subset characterised by enrichment for wild-type TP53, Caspase-8 mutations, and low copy number alterations.

On the basis of these insights, the study team developed a clinical study to revisit farnesyltransferase inhibitor as a therapeutic strategy to target mutant HRAS in human malignancies. Tipifarnib is a first-in-class non-peptidomimetic quinolinone that binds and potently inhibits farnesyltransferase. Its prior clinical development consisted of more than 70 clinical studies in solid and haematologic malignancies, however conducted without genetic selection.

A single-arm, open-label phase II, KO-TIP-001 study was developed to evaluate the ORR of tipifarnib in patients with incurable HRAS mutant solid tumours. The study team enrolled 30 patients with R/M HNSCC; one additional patient was treated on an expanded access programme. After an ad hoc analysis of the first 16 patients with HNSCC with mutant HRAS variant allele frequency data, enrolment was limited to those with a mutant HRAS variant allele frequency of ≥20%. The primary endpoint was ORR. Secondary endpoints included assessing safety and tolerability.

Patients received tipifarnib 600 or 900 mg orally twice daily on days 1-7 and 15-21 of 28-day cycles. Of the 22 patients with HNSCC with high variant allele frequency, 20 were evaluable for response at the time of data cut-off.

The ORR for evaluable HNSCC patients with variant allele frequency was 55% (95% confidence interval [CI] 31.5 to 76.9). Median PFS on tipifarnib was 5.6 months (95% CI 3.6 to 16.4) versus 3.6 months (95% CI 1.3 to 5.2) on last prior therapy. Median OS was 15.4 months (95% CI 7.0 to 29.7).

The most frequent treatment-emergent adverse events among the 30 patients with HNSCC were anaemia (37%) and lymphopenia (13%).

The authors wrote that main caveats of this study include the non-randomised, open-label design and the small sample size. However, the efficacy signal observed is impressive for a targeted therapy in a biomarker-selected HNSCC patient cohort and supports continued investigation of tipifarnib.

A pivotal AIM-HN and SEQ-HN Study evaluating the efficacy and safety of tipifarnib in HRAS mutant HNSCC (AIM-HN) and the impact of HRAS mutations on HNSCC therapies (SEQ-HN) is currently ongoing.

Alexander T. Pearson and Everett E. Vokes of the The University of Chicago wrote in accompanied editorial that clinical responses in this study represent potentially impactful change in clinical HNSCC research. It is novel because of a limited number of current successful targeting strategies for RAS family alterations and few targeted treatment strategies in HNSCC. The ideal patients for tipifarnib treatment will likely become more apparent as more data are collected. They also wrote that the development of targeted therapies in HNSCC has been slow and they hope that these results will help to further justify increased clinical genomic testing and drive translational investigations.

The study was supported by research funding from Kura Oncology.




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

Βρείτε μας

2,449ΥποστηρικτέςΚάντε Like

Διαβαστε Επίσης

Καρκίνος και Κορωνοϊός (COVID-19) ΜΕΡΟΣ Α

Εάν είστε καρκινοπαθής, το ανοσοποιητικό σας σύστημα μπορεί να μην είναι τόσο ισχυρό όσο κανονικά, έτσι μπορεί να ανησυχείτε για τους κινδύνους που σχετίζονται...


Η Παγκόσμια Ημέρα Κατά του Καρκίνου καθιερώθηκε με πρωτοβουλία της Διεθνούς Ένωσης κατά του Καρκίνου (UICC), που εκπροσωπεί 800 οργανώσεις σε 155 χώρες του...


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...
- Advertisment -

Ροή Ειδήσεων

Combining existing drugs improves prostate cancer survival

Adding abiraterone to standard hormone therapy improves survival for men with high-risk prostate cancer that’s not spread elsewhere in the body. “Today’s results are the...

New Combination of Old Drugs Improves Survival in Patients with Prostate Cancer [ESMO Congress 2021 Press Release]

LBA4_PR - Abiraterone acetate plus prednisolone (AAP) with or without enzalutamide (ENZ) added to androgen deprivation therapy (ADT) compared to ADT alone for men...

Immunotherapy Prolongs Survival in Recurrent, Persistent or Metastatic Cervical Cancer [ESMO Congress 2021 Press Release]

LBA2_PR - Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for persistent, recurrent, or metastatic cervical cancer: Randomized, double-blind, phase 3 KEYNOTE-826 study N. Colombo1, C....

Woman Diagnosed with Breast Cancer at 33 Launches Self-Examination App

Jessica Baladad has had a long history with self-examinations after a breast cancer scare in her early 20s. This habit helped save her life,...

Extended Adjuvant Treatment with Letrozole Results in Longer Survival in Postmenopausal Patients with Breast Cancer

According to results from a prospective, open-label, phase III study conducted in 69 Italian hospitals within the Gruppo Italiano Mammella among the postmenopausal patients...

Foodie Fridays: Apple Bok Choy Salad

While the temps may still be in the 80’s, apple season is upon us! Give this Apple Bok Choy salad a try!  It is...