Αρχική World News Significantly Longer PFS with First-line Pembrolizumab for MSI-H/dMMR mCRC

Significantly Longer PFS with First-line Pembrolizumab for MSI-H/dMMR mCRC

The KEYNOTE-177 study investigators reported on 3 December 2020 in The New England Journal of Medicine that the study data represent another step forward for biomarker-driven studies targeting colorectal cancer (CRC) in patients with microsatellite-instable (MSI) tumours. In particular, first-line treatment with pembrolizumab led to significantly longer progression-free survival (PFS) and fewer treatment-related adverse events (TRAEs) than chemotherapy. 

The authors wrote that programmed death 1 (PD-1) blockade has clinical benefit in MSI–high (MSI-H) or mismatch-repair–deficient (dMMR) tumours after previous therapy. It has emerged as effective therapy for MSI-H/dMMR metastatic CRC (mCRC) refractory to standard chemotherapy combinations. 

One genetic subset of CRC is tumours with dMMR, which are found in 15% of all patients with CRC of whom 12% are sporadic and 3% are hereditary cases. Approximately 80% of cases with sporadic dMMR CRC are caused by methylation of the MLH1 gene promoter, while more than 70% of hereditary cases are associated with germline mutations in the MLH1 and MSH2 genes. Both forms result in the inability of cells to recognise and repair spontaneous mutations, resulting in a very high tumour mutation burden as well as altered microsatellite sequences that render these tumours high in MSI. 

Randomised, phase III, open-label KEYNOTE-177 study (NCT02563002) was conducted to evaluate the efficacy and safety of PD-1 blockade with pembrolizumab compared with standard of care chemotherapy as first-line treatment for MSI-H/dMMR mCRC. In total, 307 patients with MSI-H/dMMR treatment naïve mCRC were randomly assigned in a 1:1 ratio, to receive pembrolizumab every 3 weeks or 5-fluorouracil–based chemotherapy with or without bevacizumab or cetuximab every 2 weeks. Patients who received chemotherapy could cross over to pembrolizumab after disease progression. The study primary endpoints were PFS and overall survival (OS). 

At the second interim analysis, after a median follow-up (calculated from randomisation to data cut-off) of 32.4 months (range, 24.0 to 48.3), pembrolizumab was superior to chemotherapy in terms of PFS (median, 16.5 vs. 8.2 months; hazard ratio, 0.60; 95% confidence interval 0.45 to 0.80; p = 0.0002). 

The estimated restricted mean survival after 24 months of follow-up was 13.7 months (range, 12.0 to 15.4) as compared with 10.8 months (range, 9.4 to 12.2). As of the data cut-off date, 56 patients in the pembrolizumab group and 69 in the chemotherapy group had died. Data on OS were still evolving with 66% of required events occurred and remain blinded until the final analysis. 

An overall response (complete or partial response) evaluated according RECIST v1.1 was observed in 43.8% of the patients in the pembrolizumab group and 33.1% in the chemotherapy group. Among patients with an overall response, 83% in the pembrolizumab group compared with 35% of patients in the chemotherapy group had ongoing responses at 24 months. 

The authors wrote that benefit was observed across key patient subgroups and supports previous data showing the benefit of pembrolizumab monotherapy in MSI-H/dMMR solid tumours. 

Grade 3 or higher TRAEs  occurred in 22% of the patients in the pembrolizumab group compared with 66% (including one patient who died) in the chemotherapy group. 

Improved PFS observed in KEYNOTE-177 study was reflected by clinically meaningful improvements in health-related quality of life that favoured pembrolizumab over chemotherapy, according to findings presented recently at the ESMO Virtual Congress 2020

Axel Grothey wrote in an accompanied editorial article that the durability of response, better safety profile, and improved quality of life associated with immune checkpoint blockade compared with chemotherapy make pembrolizumab the preferred choice of treatment in MSI-H/dMMR mCRC. The KEYNOTE-177 study findings support ongoing studies investigating immune checkpoint inhibitors in the adjuvant and neoadjuvant settings. However, the ultimate goal would be to find active treatment approaches for patients with microsatellite-stable, mismatch repair–proficient tumours that constitute the majority of mCRC cases. 

The KEYNOTE-177 study was supported by Merck Sharp and Dohme and by a Stand Up to Cancer Colorectal Cancer Dream Team Translational Research Grant. 

References

 André T, Shiu K-K, Kim, TW, et al. Pembrolizumab in Microsatellite-Instability–High Advanced Colorectal Cancer. N Engl J Med 2020;383:2207-18. DOI: 10.1056/NEJMoa2017699. 

Grothey A. Pembrolizumab in MSI-H–dMMR Advanced Colorectal Cancer — A New Standard of Care. N Engl J Med 2020; 383:2283-2285. DOI: 10.1056/NEJMe2031294.

Source

NEWSLETTER

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

Βρείτε μας

2,449ΥποστηρικτέςΚάντε Like
57ΑκόλουθοιΑκολουθήστε

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...

ΠΑΓΚΟΣΜΙΑ ΗΜΕΡΑ ΚΑΡΚΙΝΟΥ

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)

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

10 Ways You Can Nurture A More Sustainable Garden

Sustainable gardening doesn’t have a firm, technical definition. It’s the concept of using sustainable gardening techniques that not only cause no harm to the...

Cancer Research UK spin-out gets US approval to trial unique T cell therapy

Cancer Research UK’s spin-out, GammaDelta Therapeutics (‘GammaDelta’), has been given approval from the US Food and Drug Administration (FDA) to trial its unique T-cell...

Platinum-Based Chemotherapy Versus Capecitabine in Patients With Residual TNBC Following Neoadjuvant Chemotherapy

The ECOG-ACRIN EA1131 study hypothesised that invasive disease-free survival (iDFS) would not be inferior but improved in patients with basal subtype triple-negative breast cancer...

Adding Checkpoint Inhibition to Anti-HER2 Breast Cancer Therapy Brings no Benefit [ESMO Virtual Plenary Press Release]

VP6-2021 - IMpassion050: A phase III study of neoadjuvant atezolizumab + pertuzumab + trastuzumab + chemotherapy (neoadj A + PH + CT) in high-risk,...

Breaking News: Supreme Court Upholds the Affordable Care Act

It’s a great day for cancer survivors. The Supreme Court of the United States (SCOTUS) upheld the Affordable Care Act (ACA), commonly known as...

How Does CAR T-Cell Therapy Work in Treating Cancer?

Craig A. Portell, MD, is an Associate Professor of Medicine at the University of Virginia and a member of the UVA Cancer Center in...