Gene-Guided Immunotherapy Misses Mark in Recurrent/Metastatic Head and Neck Cancer

— Few actions with or without assistance in little primary step for “individualized” treatment

by
Charles BankheadSenior Editor, MedPage Today
March 4, 2024

Gene-guided treatment choice for recurrent/metastatic head and neck squamous cell cancer (HNSCC) stopped working to enhance illness control versus random treatment choice in a little initial medical trial.

Individualized treatment directed by immune gene expression attained illness control in 2 of 6 clients as compared to 3 of 12 clients who got randomized treatment. The mathematical distinction in between the 2 groups did not attain analytical significance, although illness control lasted more than two times as long in clients who got treatment by gene expression assistance.

The trial showed continuous efforts to enhance treatment choices for clients with sophisticated head and neck cancer that has actually advanced on previous immuno-oncology (IO) routines, reported Dan Zandberg, MD, of the UPMC Hillman Cancer Center in Pittsburgh, at the Multidisciplinary Head and Neck Cancers Symposium in Phoenix.

“Efficacy overall was low … in immuno-oncology failure clients,” stated Zandberg. “Prospective choice was possible, and picked clients had a numerically greater DCR [disease control rate]with a longer period of steady illness. Additional correlative analysis of this friend is continuous.”

“This represents a little primary step towards a more individualized method to treatment with immunotherapy,” he included.

The detectives utilized a special approach that depend on rapid-turnaround gene expression profiling of LAG3 and CTLA4 with the OmniSeq Immune Report Card (IRC) to direct drug choice, composed Christopher Wilke, MD, PhD, and Yvonne Mowery, MD, PhD, likewise of the Hillman Cancer Center, in a composed summary of the discussion. The IRC catches expression of 397 genes, reported as a relative rank rating (RRS) for each gene compared to a referral population.

“This abstract is considerable for its pioneering effort to present a tailored treatment choice method based upon immune gene expression in R/M [recurrent/metastatic] HNSCC,” kept in mind Wilke and Mowery, who were not private investigators in the trial. “The research study’s findings add to the developing landscape of accuracy medication, which holds pledge for enhancing results in this difficult medical circumstance. This platform might be extended to other illness websites and to consist of other targeted immune-based rehabs.”

Immunotherapy has actually enhanced results for clients with HNSCC and presently represents the requirement of look after recurrent/metastatic HNSCC. Clients whose illness advances on anti-PD-1 treatment have actually restricted treatment choices. Usage of growth gene expression to guide treatment choices has actually brought in substantial interest amongst oncology scientists. Zandberg reported findings from a stage II trial of growth gene expression to choose treatment in the post-immunotherapy setting of recurrent/metastatic HNSCC.

Qualified clients had illness that advanced on a previous IO routine and had actually gotten no greater than 3 lines of systemic treatment for HNSCC. Detectives evaluated biopsy specimens with the IRC, which reports findings as an RRS of expression of each gene compared to a referral population, stabilized to a worth of 1-100.

In this trial, an RRS ≥ 15.2 for CTLA4 versus LAG3 “chosen” a client to get nivolumab (Opdivo) plus ipilimumab (Yervoy). If the outcome was reversed (LAG3 > CTLA4a client got nivolumab plus relatlimab (Opdualag). If the RRS distinction was << 15.2, clients were randomized to the 2 programs. The main endpoint was unbiased reaction rate (ORR).

The 18 evaluable clients had an average age of 64, and males represented all however one client. The most main websites of cancer were the oropharynx (61%, 91% HPV favorable) and throat (22%). Best reaction to prior anti-PD-1 treatment (with or without chemotherapy) was partial reaction in 6 clients and steady illness in 6 others.

Gene expression results chosen 6 clients to get nivolumab and relatlimab (none for nivolumab/ipilimumab), and the staying 12 were randomized to the 2 programs. Consequently, an overall of 11 clients got nivolumab/relatlimab and 7 got nivolumab/ipilimumab, which produced a DCR of 27%. Typical period of illness control in all 18 clients was 53 days.

Nivolumab-relatlimab resulted in a DCR of 33% in the 6 clients chosen for the program by gene expression and 25% in the 12 clients randomized to the 2 routines. Mean period of illness control was 133.5 days with nivolumab/relatlimab versus 55 days for the 12 randomized clients.

A gene expression analysis revealed that KRT5 and TRIM29 were the only genes extremely revealed in >> 90% of clients. 7 genes were extremely revealed in >> 50% of clients, and 5 displayed low expression in >> 90% of clients. Possibly scientifically pertinent genes or that are currently targeted were TRIM29; EGFR, GITRand TGFB1 (extremely revealed in >> 50%); and KIR2DL1 (low expression in >> 90%).

Gene expression varied in between clients formerly treated with anti-PD-1 treatment versus chemotherapy. A greater percentage of clients treated with anti-PD-1 revealed TGFB1 (P=0.04). A greater percentage of clients treated with chemotherapy had high expression of GNLY OAS1 IFIT3 IDO2and IL12B (P< 0.05).