Neoadjuvant Immunotherapy Does Not Find Its Place Yet in Resectable NSCLC

Two phase II trials of neoadjuvant immunotherapy with checkpoint inhibitors in patients with non-N2, resectable non-small-cell lung cancer (NSCLC) reported unexpected results at ESMO Virtual Congress 2020.

The IFCT-1601 IONESCO trial of neoadjuvant durvalumab was stopped early owing to an excess in 90-day postoperative mortality (Abstract 1214O). Patients received 3 courses of durvalumab followed by surgical resection between days 2 and 14 after the last infusion. In 46 eligible patients, 4 (9%) deaths were recorded. Overall, 41 out of 46 (90%) patients achieved the primary endpoint of complete surgical resection (R0 resection); 4 patients had a partial response, 36 had stable disease and 6 had progressive disease. Median overall survival and disease-free survival were not reached. No grade 3–5 durvalumab-related adverse events were recorded.

In the second study, the PRINCEPS trial, the efficacy and safety of one dose of neoadjuvant atezolizumab, followed by surgery between day 21 and 28, was investigated (Abstract 1215O). No major pathological responses (≤10% viable tumour) or radiological responses were reported. Of the 30 patients enrolled, all had planned surgery, no patients had surgery delayed by >15 days and 29 had R0 resection. In total, 20 of 29 patients had histopathological features of response, including immune activation, tissue repair and/or tumour cell death.

Prof. Isabelle Opitz, Director of the Department of Thoracic Surgery of the University Hospital Zurich, Switzerland and Chair of the Lung Cancer Center Zurich, believes that while the results may appear intriguing, there is a lot to learn from these studies. “Both trials are early phase clinical trials and it may be premature to suggest halting further investigation of these drugs on the basis of these data. We need to be aware that the results may be related not just to drug activity but also to study design or to patient inclusion criteria,” she says. “For example, we should not overlook the fact that there were responses in the IONESCO trial. Yes, the mortality appears high. However, the patients enrolled had relevant comorbidities such as cardiovascular conditions. In addition, there was a high rate of pneumonectomies (9 patients), which is known to be a factor associated with higher morbidity and mortality.” She suggests that the results of the PRINCEPS trial may, to some extent, reflect insufficient treatment, since “patients received only one dose of atezolizumab prior to surgery.”

Opitz thinks that neoadjuvant immunotherapy has a place in this setting but that we need more data. “Our centre has been involved with several trials of immunotherapy and immunochemotherapy induction and has a positive experience in terms of surgical morbidity and mortality,” she says, adding, “The results of ongoing studies investigating durvalumab or atezolizumab as monotherapy or in combination with chemotherapy will help defining the place for these agents on patients’ treatment pathway.”

Abstracts and sessions details

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