Immunotherapy in NSCLC in difficult-to-treat populations

During  ESMO 2023 MediMIx had the honour to organise a discussion on immunotherapy in NSCLC in difficult-to-treat populations with Prof Dirk De Ruysscher (UMC Maastricht) and Dr Lizza Hendriks (UMC Maastricht). This discussion was moderated by Prof Johan Vansteenkiste (UZ Leuven).

One of the central topics of discussion was the selection of immunotherapy regimens in the absence of PD-L1 expression, particularly in patients with squamous cell carcinoma and adenocarcinoma. The consensus among experts is that for patients with squamous cell carcinoma in stage IV without PD-L1 expression, the CheckMate 9LA regimen is a preferred choice, assuming it is well-tolerated. However, the decision becomes more complex when dealing with adenocarcinoma patients lacking PD-L1 expression. In such cases, extensive NGS to identify driver mutations becomes crucial. While patients with PD-L1-negative adenocarcinoma may still benefit from immunotherapy, the magnitude of this benefit tends to be less pronounced than in PD-L1-positive patients. Clinical trial data on the efficacy of immunotherapy in PD-L1-negative adenocarcinoma is not as robust as in squamous cell carcinoma, making treatment decisions challenging.

Regarding patients with stage IV NSCLC and brain metastasis, the historical approach involved administering local radiotherapy before immunotherapy, as it was believed that immunotherapy had limited efficacy within the brain. However, emerging evidence suggests that immunotherapy can be effective in brain metastases as well. Whether to prioritise radiotherapy now depends on factors like the number, volume, location, and symptoms of brain metastases. Patients with asymptomatic brain metastases in non-eloquent areas are candidates for immunotherapy, either as monotherapy or chemo-immunotherapy. The importance of comprehensive imaging for both intracranial and extracranial disease monitoring is emphasised. Symptomatic brain metastases continue to warrant immediate local treatment, often through stereotactic radiation or surgery.

Patients with both stage IV lung cancer and HIV represent a unique challenge in clinical practice. Historically, concerns arose about the safety of administering immunotherapy to such patients or enrolling them in clinical trials. However, recent phase 1 and phase 2 trials have provided evidence that patients with controlled HIV, adequate CD4 counts, and well-managed antiretroviral therapy can safely receive immunotherapy. Data suggest that HIV-positive patients benefit from immunotherapy similarly to HIV-negative patients. In chemotherapy cases, consideration of drug-drug interactions is necessary, and consultation with an infectious disease specialist is recommended.

When patients receiving immunotherapy (monotherapy) with high PD-L1 expression experience disease progression, the appropriate course of action remains under investigation. Early data generated hypotheses about the potential benefits of continuing immunotherapy alongside platinum-doublet chemotherapy. Further research is needed to clarify which patient profiles may benefit most from this strategy, considering factors like fitness, reimbursement, and clinical outcomes.

In summary, this discussion on immunotherapy in metastatic NSCLC provided valuable insights into the practical application of immunotherapy in different-to-treat populations. The dynamic landscape of immunotherapy continues to evolve, and these discussions shed light on the complexities and challenges clinicians face in making treatment decisions for lung cancer patients. More clinical research and data are essential to refine further and individualise treatment approaches.