medwireNews: Two phase 2 studies presented at the ESMO Virtual Congress 2020 have highlighted the risks and benefits of neoadjuvant immunotherapy in patients with resectable non-small-cell lung cancer (NSCLC).
The IONESCO study, presented by Marie Wislez, from Hôpital Cochin in Paris, France, involved 46 patients (median age 61 years, 67% men) with stage IB (>4 cm) to IIIA, non-N2 disease, who received three doses of durvalumab 750 mg on days 1, 15, and 29, followed by resection between 2 and 14 days after the last infusion.
The primary endpoint of complete surgical resection was achieved by 89.1% of the study participants, but the study was stopped early due to excessive 90-day postoperative mortality.
There were four (9%) deaths during this period that were “due to postoperative complications most likely related to comorbidities and not to direct durvalumab toxicity,” Wislez said. Indeed, three of the four patients had arterial hypertension in combination with peripheral arterial disease, ischemic heart disease, severe chronic obstructive pulmonary disease, or diabetes.
One of the four deaths was due to surgical complications at 45 days, one was due to acute respiratory failure at 21 days, one was due to a tracheal fistula at 8 days, and one was a sudden death that occurred at home 40 days after surgery.
Wislez said “this highlights the necessity to be very cautious with comorbidities in neoadjuvant clinical trials and perhaps especially for durvalumab.”
Among the other outcomes measured, the partial response rate was 8.7% and the major pathologic response (MPR; ≤10% residual viable tumor cells) rate was 18.6%, with MPR significantly associated with disease-free survival.
Specifically, all patients with an MPR were alive and relapse-free at 12 months, compared with a significantly lower 77.1% of those without an MPR.
The PRINCEPS study, presented by Benjamin Besse, from Gustave Roussy in Villejuif, France, involved 30 patients (mean age 64 years, 50% men) with clinical stage I (≥2 cm) to IIIA NSCLC who received a single atezolizumab 1200 mg injection followed by surgery 21 to 28 days later.
In this analysis, the primary endpoint was the 2-month tolerance rate, defined as the proportion of patients without major toxicity or morbidity between the start of treatment and 1 month after surgery.
Besse reported that none of the patients experienced a surgical delay of more than 15 days – one of the criteria of major toxicity – but seven (23%) had a grade 1–3 complication in the month following surgery. These included respiratory distress and septic shock, paresthesia, atrioventricular heart block, atrial fibrillation, and bronchial congestion.
All but one patient (97%) underwent complete resection, two patients (7%) had a partial response, and 14% had an MPR.
Correlation analyses indicated that MPR was not significantly linked to RECIST response or metabolic variations, but was significantly and positively associated with PD-L1 expression.
Besse concluded that “one cycle of preoperative atezolizumab was safe and did not impair surgery.”
Discussant Lyudmila Bazhenova, from the University of California San Diego in the USA, praised the two studies and said that “neoadjuvant immunotherapy […] has shown encouraging results” in an area of large unmet need but that many questions remain.
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ESMO Virtual Congress 2020: 19–21 September (Abstract 1214O)
ESMO Virtual Congress 2020: 19–21 September (Abstract 1215O)