Long-Term Immune Checkpoint Inhibition Shows Potential Extended Survival in NSCLC

Holographic concept of lung cancer: © catalin - stock.adobe.com

Clinical trials of immune checkpoint inhibitors (ICIs) have set a standard of 2 years of therapy; however, it remains unclear if longer exposure to these agents has any benefit. A retrospective study investigated the long-term outcomes of patients with metastatic non–small cell lung cancer (NSCLC) treated with ICIs for at least 2 years.

The results show that patients who received ICIs for at least 2 years experienced significantly longer survival compared with historical standards. Surprisingly, there was no difference in outcomes between patients who continued ICIs beyond2 years and those who stopped after 2 years.

Even after disease progression following prolonged ICI treatment, a substantial number of patients responded to ICI retreatment. Factors associated with a higher likelihood of response to ICI retreatment included longer initial ICI treatment duration, higher tumor mutational burden, and adenocarcinoma histology.

These findings suggest that ICI can provide long-term benefits for patients with NSCLC and that ICI retreatment may be a viable option for patients who progress after initial therapy.

In an interview with Targeted Oncology, Biagio Ricciuti, MD, thoracic medical oncologist at Dana-Farber Cancer Institute in Boston, Massachusetts, discussed these findings and their implications for treatment guidelines in this patient population.

Biagio Ricciuti, MD

Targeted Oncology: What are the unmet needs in the patient population that this study focused on?

Ricciuti: Immunotherapy has changed the treatment landscape for patients with non–small cell lung cancer and can produce very durable responses. However, one of the questions that is still open is, what is the optimal duration of immunotherapy for these patients? Recent, randomized studies have capped the treatment duration to 2 years, and so this is what we generally do. We stop immunotherapy after 2 years of treatment if there is no evidence of disease progression. But what is unclear is whether there are patients that may benefit from extended immunotherapy beyond those 2 years.

What was this study evaluating?

This was a global retrospective study accruing patients who received immunotherapy for a minimum of 2 years across Europe, the United States, and South America. The goal was to understand whether a fraction of these patients who received immunotherapy for at least 2 years benefited from indefinite vs fixed duration of this treatment.

Can you summarize the findings?

We accrued 421 patients who received a minimum 2 years of immunotherapy, and we looked at the question, what is the clinical outcome of the patients who stopped at 2 years vs those who continued beyond the 2 years of treatment? In general, in the entire cohort, the median progression-free survival was 7 years, which was unprecedented, and so this was interesting for us to understand. Second, the overall survival in the cohort was about 9 years. Again, extremely long survival for patients with metastatic, non–small cell lung cancer.

The goal was to look at a subset of patients that could potentially benefit more from extended immunotherapy. What we found in this study is that patients with low PD-1 expression, low mutational burden, as well as those patients with a stable disease as best response to immunotherapy, had a faster occurrence after stopping immunotherapy, suggesting that potentially, there are subsets of patients that may indeed benefit from indefinite or extended immunotherapy.

What are the implications of these findings?

The implications of this study are that there is a fraction of patients with non–small cell lung cancer who have completed years of treatment that may benefit from extended immunotherapy. We really need to think about specific features that may help us predicting who is going to be at risk of recurrence after stopping immunotherapy and for these patients, we should put in place treatment options that can potentially extend their benefits, such as continuing immunotherapy indefinitely.

On the other hand, the other implication is that there is a fraction of patients instead that will do well after stopping immunotherapy. For those patients, there is no need for further immunotherapy. Overall, these data will help us guide treatment decisions at that 2-year juncture.

What are the next steps in this research?

I think the next step is to better understand the patients with the greatest likelihood of responding to immunotherapy. So far, we do know that only 50% of our patients will respond to these treatments, and we do not have a clear consensus of the strongest, more robust predictive biomarkers of response to immunotherapy. We do know that PD-1 expression is important. We do know that mutational burden is important. But what is now becoming increasingly relevant is the genomic profile of our patients. There is a wide spectrum of communication and mutation that can occur in patients with non–small cell lung cancer that can predict response or resistance to immunotherapy, and we really need to start leveraging that information to optimize treatment selection with currently approved immunotherapies.

REFERENCE:

Ricciuti B, Gariazzo E, Gorria T, et al. Clinical outcomes and post-progression retreatment in patients with metastatic NSCLC who complete two years of treatment with immune checkpoint blockade.J Clin Oncol. 2024;42(suppl 16):abstr 8633. doi:10.1200/JCO.2024.42.16_suppl.8633