The tumor mutational burden has emerged as a potential biomarker of benefit to asses which patients are suitable for a specific treatment. There was a study, Hellman et al 2018, in which they measured the efficacy of Nivolumab plus Ipilimumab in patients with non-small cell lung cancer (NSCLC) in a phase 3 trial. They examined progression-free survival of the immunotherapy mentioned above vs chemotherapy among patients with a high tumor mutational burden (more or equal to 10 mutations per base).
The population studied in the trial, were stage IV NSCLC patients that never received chemotherapy. They were randomly assigned into two groups:
- In a 1:1:1 ratio those who had at least 1% expression level of the tumor programmed death ligand 1 (PDL-1)
- In a 1:1:1 ratio those who had a less than 1% expression level of PDL-1
The options for both arms were: Nivolumab plus Ipilimumab, Nivolumab monotherapy or chemotherapy.
Surprisingly, was significantly longer the progression-free survival among patients with a high tumor mutational burden. For the 1 year progression-free survival rate, the patients who were in the arm of Nivolumab plus Ipilimumab had the higher rate with a 42.6% of survival, compared to the other treatment options. Moreover, the benefit of Nivolumab plus Ipilimumab was more consistent within subgroups over chemotherapy; including patients with at least 1% expression level of PDL-1 or the ones who had less than 1% expression level. The benefit was also seen in the rate of adverse events, which the ones that were grade 3 or 4 were more common in the chemotherapy group with a 36.1% compared to the immunotherapy who had 31.2%.
These results validate the benefit of Immunotherapy (Nivolumab + Ipilimumab) in NSCLC, and that the progression free survival rate was significantly longer in this group compared to the chemotherapy group, having not much impact the PDL-1 expression level. In the other hand the Tumor Mutational Burden (TMB), in concert with PDL-1 expression, has been demonstrated to be a useful biomarker; however further validations studies are required.
Here in Althian we have several trials working with the immunotherapy mentioned in paragraphs above, so we know about the most common adverse events related to these molecules. We have staff that is more than qualified to manage these complicated trials. Please contact us and we will be more than happy to assist you.
Image from Genetic Engineering and Biotechnology News