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2 Pembrolizumab Trials in Head and Neck Cancer Yield Divergent Results

Meeting Coverage > > MHNCS– One first-line routine caused even worse OS, while another uses an extra alternative

by Mike Bassett, Staff Writer, MedPage Today March 1, 2024

2 first-line trials including pembrolizumab (Keytruda)-based mixes for the treatment of frequent or metastatic head and neck squamous cell cancer (HNSCC) provided blended outcomes.

While first-line pembrolizumab plus lenvatinib (Lenvima) considerably enhanced progression-free survival (PFS) and general action rate (ORR) compared to pembrolizumab alone in clients with frequent or metastatic HNSCC with PD-L1 integrated favorable rating ≥ 1, it stopped working to enhance general survival (OS), reported Lisa Licitra, MD, of the University of Milan.

In the other research study, a pembrolizumab-based program that changes the chemotherapy foundation of platinum and fluorouracil with carboplatin and paclitaxel accomplished outcomes “constant with other first-line routines in this client population consisting of the standard-of-care mix of pembrolizumab plus platinum and fluorouracil,” stated Marcin Dzienis, MD, of Gold Coast University Hospital in Brisbane, Australia.

Both research studies existed at the Multidisciplinary Head and Neck Cancers Symposium in Phoenix.

LEAP-010

The stage III LEAP-010 trial randomized 511 clients to pembrolizumab plus lenvatinib or pembrolizumab plus placebo.

With an average follow-up of 11.5 months, the very first interim analysis revealed that the mean PFS was 6.2 months with the mix versus 2.8 months with pembrolizumab alone (HR 0.64, 95% CI 0.50-0.81, P=0.0001). The 12-month PFS rates were 28.5% and 19.2%, respectively.

The ORR was 46.1% with the mix and 25.4% with pembrolizumab alone (P=0.00003).

In a 2nd interim analysis at a typical follow-up of 21.3 months, mean OS was simply 15 months with the mix versus 17.9 months with pembrolizumab alone (HR 1.15, 95% CI 0.91-1.45, P=0.882), with 24-month OS rates of 36% and 40%, respectively.

When it comes to security, 61.4% of clients in the mix arm had grade ≥ 3 treatment-related unfavorable occasions (TRAEs) compared to 17.8% in the pembrolizumab-alone arm, with 28% and 8%, respectively, ceasing treatment due to TRAEs.

There were 10 treatment-related deaths– 7 in the mix arm and 3 in the pembrolizumab-alone arm.

The outcomes recommend that first-line pembrolizumab as monotherapy or in mix with chemotherapy “stays the requirement of take care of first-line treatment for clients with recurrent/metastatic HNSCC,” Licitra concluded.

Based upon these OS results, the research study’s sponsors closed LEAP-010.

When asked how the unfavorable arise from LEAP-010 may effect LEAP-009 (which is examining pembrolizumab plus lenvatinib versus chemotherapy in clients with frequent or metastatic HNSCC following development after platinum-based chemotherapy and immunotherapy), Licitra kept in mind that a few of the LEAP trials– such as those including other illness consisting of non-small cell lung cancer, urothelial cancer, and cancer malignancy– were likewise favorable in regards to PFS and ORR, however not in OS.

“This is something that is making us consider the truth that this mix is most likely not the very best method to go,” she stated.

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