stage 3a NSCLC with resection, chemo, and if able check point inhibitor

For resectable stage IIIA non-small cell lung cancer, neoadjuvant chemotherapy plus the immune checkpoint inhibitor nivolumab is the best option from the choices presented (choice D is correct).

The patient described has clinical stage IIIA squamous cell carcinoma (T2aN2M0). There has been a great deal of uncertainty about the best treatment for patients with stage IIIA because of N2 involvement. The role of surgical resection is informed by imperfect data. Controlled trial results have not shown evidence of improved survival for all comers with stage IIIA because of N2 involvement. Patients with a high burden of N2 disease, often defined as bulky adenopathy (>2 cm) or multistation adenopathy, and those requiring a pneumonectomy, had the poorest outcomes with surgical resection. Those with a low burden of N2 disease who required a lobectomy had better outcomes with the combination of neoadjuvant therapy than treatment with chemoradiation alone. The patient in this question has low-burden N2 disease, will require a lobectomy, and has normal cardiopulmonary fitness, so surgical resection would be recommended as part of her care (choices A and B are incorrect).

Investigators in a study published in 2022 compared outcomes in patients with surgically resectable stage IB through III non-small cell cancer treated with neoadjuvant chemotherapy with outcomes in those treated with neoadjuvant chemotherapy plus the immune checkpoint inhibitor nivolumab. Sixty-three percent of those enrolled had stage IIIA disease. Those treated with chemotherapy and nivolumab had a longer median event-free survival (31.6 vs 20.8 months) and higher pathological complete response rate (24.0% vs 2.2%). The difference was most pronounced in those with stage IIIA disease and those with a PD-L1 expression of 1% or greater. On an interim analysis of overall mortality, the hazard ratio was 0.57 (did not reach criteria for significance). Seventeen percent of those receiving the combined therapy did not undergo surgery compared with 25% of those receiving neoadjuvant chemotherapy alone. Grades 3 and 4 adverse events did not differ between the groups (choice C is incorrect).

If a patient has stage III disease that is deemed to be unresectable based on these criteria or has poor cardiopulmonary fitness, standard of care would include concurrent chemoradiotherapy followed by consolidation with durvalumab for 12 months if there is no progression after chemoradiotherapy. Investigators in a phase III trial compared consolidation with durvalumab with placebo in patients with unresectable stage III non-small cell lung cancer and no disease progression after concurrent chemoradiotherapy. Seven hundred nine patients were randomly assigned 2:1 to the durvalumab and placebo arms. Long-term analysis showed a hazard ratio of 0.72 for overall survival (5-year overall survival of 42.9% vs 33.4%) and 0.55 for progression-free survival (5-year progression-free survival of 33.1% vs 19.0%). Differences were greatest in those with PD-L1 expression of 1% or greater. These results led to a change in standard of care for patients with unresectable stage III disease.1

Footnotes

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