Thank you very much. It’s a great pleasure for me to present to you the headlines of the PACIFIC trials on behalf of all the investigators. This is a double blind, placebo-controlled phase III trial of durvalumab, a PD-L1 inhibitor, in patients treated with chemoradiation for stage 3 unresectable non-small cell lung cancer.
About one-third of the patients with lung cancer present what we call stage 3 disease which is a local regional disease, so no metastatic disease but it’s not localised either. They typically do have some extension locally and regionally. Typical treatment over the last decades has been concomitant chemoradiation and what you expect to get with this is a median PFS, progression free survival, of about nine months and about 15% of the patients are alive at five years. Considering that no major advances had occurred over the last two decades I think there’s an urgent clinical need for novel therapeutic approaches in this setting. Due to the performance of PD-1, PD-L1 inhibitors in the metastatic setting, some investigators initiated trials in earlier disease stage such as stage 3. Actually the PACIFIC trial is the first randomised trial in this setting for stage 3 patients.
Durvalumab actually is a monoclonal antibody against PD-L1 which is a protein that the tumour cells express to actually interact with this receptor here, PD-1, which is on the immune cell, the T-cell. By interacting with the PD-1 receptor it provokes an inhibitory signal that actually supresses the T-cell and avoids T-cell killing to the tumour. You actually inhibit this interaction with a monoclonal antibody, for example durvalumab, it actually inhibits this suppressive signal and therefore you enhance the immune system and you actually enhance T-cell tumour killing.
This is the design of the study. Locally advanced stage 3 patients treated with chemoradiation. If they do not progress after chemoradiation and are in good shape they have been randomised at the end of this period in a 2:1 fashion to durvalumab at standard doses every two weeks for a year versus placebo. Importantly, all patients were included in this trial so we did not select for PD-L1 expression in the tumours. The main endpoints PFS and overall survival and here we present the interim analysis for PFS; the trial is not mature for survival.
This is the main result here, this is the PFS curve, progression free survival, by an independent review committee blinded. You see there is an increase in PFS in patients treated with durvalumab as compared to placebo. We have a hazard ratio of 0.52, it’s statistically significant at 0.0001 level. What that means, that means that you decrease 48% the risk of progression all along the study period. That implies an increase in median progression free survival from 5.6 months on placebo treated patients to 16.8 in durvalumab treated patients, what I feel is a very robust and clinically significant improvement for patients.
Consistently there is an increase in response rates, 16% to 20%, and, of course, duration of response. Typical duration is less than 14 months with placebo and has not yet reached the median for patients treated with durvalumab. Consistent with that there is a decrease in the appearance of new metastatic lesions; that is true everywhere, in lymph nodes, brain or any visceral site. Consistent with prior data the safety profile is pretty favourable so there were no new signals in this setting. We found the toxicity that we previously knew in the metastatic disease setting. Some increase in the number of patients with grade 3/4 toxicity but a small increase, 26% in placebo, 30% in durvalumab. Leading this discontinuation 15% of the patients with durvalumab, 10% with placebo. If you look at the number of patients with immune side effects which are more specific for this type of drug, 24% versus 8% but considering only severe side effects, grade 3-4, 3.4% versus 2.6%. So a very mild increase in frequency and severity, a very mild toxicity profile.
So overall summary, I think this is a clear improvement in the outcome, increasing PFS, about an 11 months increase in PFS, consistent improvement in response rate and duration of response and decrease in the number of metastatic disease. As we know, the safety profile is quite favourable and those improvements are seen in all patients in this trial. Overall we think durvalumab is a promising option for patients with stage 3 non-small cell lung cancer treated with chemoradiation.
I’ll just acknowledge patients and families participating in this trial and those other investigators for many cancers all over the world. I would be very happy to take any questions at the end of the session.