Perioperative durvalumab in addition to neoadjuvant chemotherapy shows positive results in patients with stage IIIa(N2) NSCLC
Dr Sacha Rothschild - University of Basel, Basel, Switzerland
I presented the final analysis of our SAKK 16/14 trial. The SAKK 16/14 trial was a single-arm phase II trial investigating the use of perioperative durvalumab in addition to neoadjuvant chemotherapy in patients with stage 3a N2 non-small cell lung cancer.
What was the study design?
The study design, as already mentioned, it was a single-arm phase II trial for patients with stage 3a N2 disease. So all these patients had confirmed mediastinal lymph node involvement. They were treated with our current standard chemotherapy that was established in our previous trials, so the SAKK 16/00 and 16/96, with three cycles of cisplatin and docetaxel followed by two cycles of the anti-PD-L1 antibody durvalumab, followed by resection. So all these patients were deemed resectable at the beginning. They received, as mentioned, three cycles of chemotherapy, two cycles of durvalumab, were then resected and postoperatively, so in the adjuvant setting, they again received durvalumab every two weeks for one year.
The primary endpoint of the trial was event free survival after 12 months and, based on our previous findings with chemotherapy alone, with neoadjuvant chemotherapy alone, we aimed at improving 12-month event free survival from 48% to 65%.
What were the results of this study?
The primary endpoint of the trial, the one-year event free survival was clearly improved. These results have already been published in Journal of Clinical Oncology in 2021. One-year event free survival was at 73.4%, so this has already been published. Now we presented the final analysis of this trial, so the final analysis after a median follow-up period of 72 months, or six-year follow-up. So far this is beside all the other trials with perioperative immunotherapy that are now published, this is the trial with the longest follow-up in this patient population. So after a median follow-up time of 72 months we have a median event free survival of four years and a 5-year event free survival rate of 45.9%. The overall survival after the median follow-up of 72 months was not yet reached and the 5-year overall survival rate is at 65.8%.
What we were able to see is that the pathological response is an important predictor of outcome. So overall we had 18% of patients with a pCR, so a pathological complete remission, and of those patients a median event-free survival was not reached after a follow-up of six years and the 5-year event free survival rate for patients with a pCR was 71.4% and the 5-year overall survival rate in this specific subgroup of patients was 100%. Also mPR, so major pathological remission, was a predictor of outcome. So patients achieving an mPR achieved a median event free survival that was not reached after six years and a five-year event free survival rate of 65.7%.
What do you think is the clinical significance of these results?
The SAKK 16/14 trial was the first trial actually investigating neoadjuvant and perioperative checkpoint inhibitors. Now we have the results of several randomised trials so this is now a new standard of care. I think what our trial adds is now really the long-term follow-up of these patients, supporting the use of perioperative immune checkpoint inhibition and it clearly shows us that the pathological response is an important predictor. So therefore our follow-up trial, the 16/18 trial, now aims at again improving pathological response by the use of immune modulatory radiotherapy.
So on the one hand it is the basis for all the further trials that have now been published and that lead to a new standard of care, but it’s also hypothesis generating for future clinical trials in this setting.
