Two good options for patients with stage III NSCLC

The contemporary management of patients with stage III NSCLC has been one of the main talking points at the 2024 European Lung Cancer Conference. During several animated debates specialists shared their views on how to best integrate immunotherapy in the peri-operative treatment paradigm for these patients. To discuss some of the points that were raised during these debates, Dr Charlotte De Bondt, pulmonolgist and thoracic oncologist at the GZA Hospitals in Antwerp was joined by Prof Mariana Brandao, medical oncologist at the Institut Jules Bordet in Brussels.

One of the more controversial statements that was raised with respect to stage III patients suggests that it might be better to postpone the decision on whether a patient is resectable or not until after neo-adjuvant induction chemo-immunotherapy. However, for Prof Brandao and Dr Bondt, using chemo-immunotherapy for surgical downstaging is not a good idea, both for scientific and practical reasons (i.e., reimbursement restrictions). For borderline resectable patients, Prof Brandao instead argued for a dedicated multidisciplinary discussion on the available treatment options, with close involvement of the patient. If this discussion leads to the conclusion that the patient is resectable, she prefers to immediately move to surgery and follow-up with adjuvant immunotherapy. If the patient is deemed unresectable, chemoradiotherapy followed by consolidation durvalumab is still the way to go.

During ELCC 2024, several presentations underscored the challenging nature of response assessments following neoadjuvant chemo-immunotherapy. For Prof Brandao, a contrast-enhanced CT scan (e.g., PET-CT) should be a routine part of the response assessment for these patients. However, one must also take the possibility of pseudoprogression into account when dealing with these patients. In this light, there remains to be an important role for mediastinal staging following neo-adjuvant chemo-immunotherapy.

Also at ELCC 2024, results were presented of the phase III PACIFIC II trial, comparing CRT alone to durvalumab in combination with chemoradiotherapy (CRT) followed by consolidation durvalumab. Surprisingly, this trial did not show a PFS benefit for the durvalumab-based approach. For Prof Brandao a possible explanation for this negative result could be a high rate of (Asian) patients with an EGFR mutation enrolled in this trial. The study did suggest a better result with the durvalumab-CRT regimen in European patients and in patients with a smaller tumour volume.

In conclusion, we now have two good options for patients with stage III NSCLC: neo-adjuvant chemo-immunotherapy followed by surgery (with/without adjuvant immunotherapy) and CRT followed by durvalumab consolidation. The choice between the two should be steered by the resectability of the tumour, determined during a multidisciplinary tumour board, and by the preference of the individual patient.