We spoke with Dr. Julie Brahmer about how survival rates are starting to improve with the use of nivolumab in non-small cell lung cancer.
As part of our coverage of the American Association for Cancer Research [AACR] annual meeting, being held April 1st to April 5th in Washington, DC, we are speaking with Julie Brahmer MD, who is a thoracic cancer director at the Johns Hopkins University in Baltimore, Maryland who specializes in the treatment of lung cancer patients. At the AACR meeting, Dr. Brahmer presented long-term, 5-year data from a clinical trial of nivolumab, an anti-PD-1 antibody in patients with non-small cell lung cancer.
-Interviewed by Anna Azvolinsky, PhD
OncoTherapy Network: First, just as background, what is the latest on the use of PD-1 [programmed death 1] and PD-L1 [programmed death ligand 1] antibodies in the clinic for lung cancer? There are several now approved and available-is that correct?
Dr. Brahmer: Yes, now we have three PD-1 and PD-L1 antibodies available in the clinic for non-small cell lung cancer. We have pembrolizumab and nivolumab-which are both PD-1 antibodies-and then most recently atezolizumab, which is a PD-L1 antibody. All of these antibodies are approved for use in the second-line treatment setting for patients with metastatic disease. We also have an antibody that is approved for first-line use which is pembrolizumab, the PD-1 inhibitor which is now approved for first-line in patients with metastatic disease whose tumors have PD-L1 staining levels of at least 50% or greater.
OncoTherapy Network: Can you tell us about the design of the particular study you presented?
Dr. Brahmer: So, the study that I have presented at AACR is the CA209-003 study, and this is the original study where nivolumab was tested in various different populations including non-small cell lung cancer and we’ve presented the safety and efficacy data and the 3-year follow up data in the past. But this year we are presenting the 5-year follow-up in this group of patients.
So, this trial took patients with metastatic non-small cell lung cancer who had received previous chemotherapy and then randomized them to just three different doses of nivolumab and treated them for up to 2 years. We saw in this long-term follow-up that there was a 5-year overall survival in this group of about 16%. Now, again, this is in previously treated patients where typically the 5-year survival rate is 4% or less. Now, based on this data in patients who are receiving nivolumab, the 5-year overall survival is 16% and we are seeing a plateau of this survival curve between 3 and 5 years and longer, so we think if you are responding to immunotherapy in those patients with non-small cell lung cancer, that response and survival can be long-term.
OncoTherapy Network: What were the important efficacy findings?
Dr. Brahmer: I think the most important is this 5-year overall survival. We’ve never in the past been able to report long-term survival data in patients with metastatic disease other than historical data, but again, this is one of the first times we are able to in patients with metastatic disease and show that there are patients who can live a very long time when treated with these antibodies.
We also looked in this follow-up data to try to figure out whether there were any clinical characteristics different in the overall patient population that went on study versus those patients who are alive and well 5 years down the road. And there is really no difference in those characteristics of the overall population versus the 5-year survivors. We have patients who have EGFR [epidermal growth factor receptor] mutations who are in the 5-year survivor group where most previous studies showed that patients with EGFR mutations don’t do well. But that certainly is not out of the question based on this data where two patients of the 16 patients that are 5-year survivors have EGFR mutations.
Also, based on PD-L1 staining and not every patient had tumor tissue available in the study to do PD-L1 staining, but if your PD-L1 tumor status was negative, there were three patients in the 5-year survivor group. If it was positive, there were seven patients in the 5-year survivor group, but also high positive, there were those patients in the 5-year survivor group as well.
Another question is do you have to, as a patient, do you have to have side effects to actually get benefit? And this study has shown that you don’t have to have side effects to reap the long-term benefits of this type of drug. So, overall, of the 129 patients, there were 16 patients that were alive at the 5-year follow up and of the 16, 12 had partial responses and two had stable disease and two had progressive disease at best response. And of the patients who are in that group of 5-year survivors, only four of those patients required further treatment.
Interestingly, one patient had just had local progression and so the area of local progression which was a lung nodule was resected and then they haven’t received any further therapy for years. So that is quite exciting and we do show some data that at least in one patient where we had enough tumor tissue to look at, his long-term survival did seem to be associated with high tumor mutation burden. That was in one patient and we are looking at more of this type of information to see if we could predict who would be in this group in the future.
OncoTherapy Network: For you as a clinician, are there implications of these results for treating patients in the clinic?
Dr. Brahmer: Well, typically when we sit down with patients who have metastatic lung cancer and talking to them about long-term survival, in the past we have not talked about the possibility of living 5 years past the time of diagnosis. But if they do well with immunotherapy, that is a possibility and I think that gives great hope for our patients.
OncoTherapy Network: Is there additional follow-up to this study that is ongoing?
Dr. Brahmer: Yes. So, there is planned further follow-up of this study-even beyond 5 years-and we would also love to have the chance to look at these patients more in depth to try to see is there anything from a marker standpoint or a laboratory correlate standpoint that we could use to help identify those patients who would be those long-term survivors on this type of therapy. As well, is the follow-up implication of this study that in the second-line treatment setting nivolumab is approved for use where you keep the patient on treatment for long-term, as long as it is keeping the cancer under control? But, from this study that I presented here, patients were stopped at 2 years if they were doing well. And then we are seeing that those patients who stopped treatment can have long-term disease control even without receiving further treatment, so clearly something is happening in the patient where they don't require further treatment and their immune system continues to keep their cancer in check.
Oncotherapy Network: Thank you so much for joining us today, Dr. Brahmer.
Dr. Brahmer: Thank you very much.