The results of this study reinforce the idea of using this combined treatment in patients with this lung tumor subtype who are candidates for surgery. Lung cancer is the leading cause of cancer-related mortality worldwide, and within the world, Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all cases. Almost 30% of patients are susceptible to surgerybut, despite this, so far the studies carried out only provide 5-year survival data that are not very encouraging.
Recently, it has been seen that immunotherapy directed against specific targets, based on the blockade of PD-1 or PD-L1 proteins, has revolutionized the treatment of this subtype of cancer, resectable NSCLC, well administered before the operation (with a neoadjuvant approach) or after it (adjuvant). To evaluate the results of this treatment in terms of survival, the NADIM study was carried out.
“Combining the advantages of neoadjuvant and adjuvant immunotherapy within perioperative regimens has the potential to further improve long-term outcomes in the management of non-small cell lung cancer. To our knowledge, the NADIM study has been the first to evaluate the activity of perioperative chemoimmunotherapy in potentially resectable stage IIIA NSCLC and, now, within this phase II study, we have verified that it also improves long-term survival indicators. term,” stated Dr. David Gómez de Antonio, thoracic surgeon, coordinator of the Scientific Committee of the SECT and co-author of the study.
The study in 18 hospitals
The NADIM study is a multicenter, single-arm, phase 2 trial, carried out in 18 hospitals in Spain, which has assessed the eligibility of 51 patients with resectable stage IIIA NSCLC, over 18 years of age, of whom 46 were finally patients with intent to treat, that is, those who could be offered the treatment.
Of these patients, 36 (74% of the sample) were men and 12 (26%) were women, with a median age of 63 years. The follow-up of the patients concluded after 5 years (60 months) and the cut-off date to begin the analysis of the results was July 11, 2023.
Before surgery, patients received neoadjuvant treatment consisting of three cycles of chemotherapy combined with a type of immunotherapy, nivolumab (360 mg). The patients then underwent surgery to remove the lung tumor and, after surgery, were given adjuvant treatment with intravenous nivolumab monotherapy for one year.
The primary endpoint studied was progression-free survival at 24 months. Secondary objectives of the study included 5-year progression-free survival, overall survival, and toxicity profile.
Five-year survival of 68%
The progression-free survival of the study population at 5 years was 65%, while the overall survival was 69.3%. These survival rates were accompanied by a high rate of complete pathological responses. However, disease progression occurred in 11 of the patients, 24% of the sample, and 14 patients (30%) died, including nine
(20%) due to disease relapse and five (11%) due to causes not related to the tumor.
Regarding toxicity, treatment-related adverse events occurred in 14 patients (30%) of 46 during neoadjuvant treatment, and in seven (19%) of 37 during adjuvant treatment. The most common adverse effects, rated grade 3 or higher, were an increase in lipase – an enzyme produced by the pancreas to break down fat in food – and febrile neutropenia – a decrease in neutrophils, a type of white blood cell. or defense cells. Each of these adverse effects occurred in 3 patients (7% of the sample).
Another notable aspect of this study is that no treatment-related surgical delays, deaths, or unexpected long-term toxicities were reported.
Booster for perioperative immunotherapy
“Until now we had seen that perioperative immunotherapy improved short-term outcomes in resectable non-small cell lung cancer.
We have now reported on the 5-year survival from the NADIM trial to evaluate its long-term benefit, and what we have seen is that perioperative chemoimmunotherapy has promising long-term benefit
no worrying safety data, reinforcing its use in lung cancer
of non-small cells in resectable stage IIIA”, highlights Dr. Gómez de
Antonio.
Specifically, perioperative chemoimmunotherapy in potentially resectable non-small cell cancer had resulted, in the shorter term, within the NADIM study, in a 2-year progression-free survival of 77.1% and a 2-year overall survival. 36 months of 81.9% in the intention-to-treat population, with overall survival at 36 months increasing to 91.0% in the per-protocol population.
These survival rates were accompanied by a high rate of complete pathological responses. Likewise, previous trials have demonstrated a median event-free survival of no more than 15 months and a 3-year overall survival of 35% with neoadjuvant chemotherapy.
Now, “the randomized phase 2 NADIM II trial has shown favorable efficacy in terms of pathological complete response, progression-free survival and overall survival with the combination of chemotherapy and immunotherapy in the long-term perioperative setting, which strengthens the idea that we should use immunotherapy in patients with non-small cell lung cancer before and after surgery,” summarizes Dr. Gómez de Antonio.
