ECC 2015

Atezolizumab monotherapy vs docetaxel in 2nd and 3rd line NSCLC

Prof Johan Vansteenkiste - University Hospital Leuven, Leuven, Belgium

Johan, first tell me all your details, where you work and what you’re doing.

Yes, hello. I’m Johan Vansteenkiste, I’m a respiratory oncologist working in the University Hospital in Leuven, Belgium in the clinical department and in the clinical trial unit for respiratory oncology.

I know you have a lot of interests but right now you’ve been taking a big interest in a new way of treating non-small cell lung cancer involving one of these checkpoint inhibitors. Tell me what you’ve been doing.

Yes, well it’s an important thing nowadays for many people, immunotherapy to treat cancer. So what we have done in the POPLAR study presented here at the European Cancer Conference is looking at, in a randomised way, a treatment for patients with relapsed lung cancer, comparing the standard, docetaxel chemotherapy, with the new immunotherapy based on atezolizumab which is an anti-PD-L1 monoclonal antibody in a comparative trial of phase II randomised comparison but almost 300 patients. So we had an interim analysis of the study before but this is the primary analysis looking at efficacy, safety and predictive biomarkers.

And did you have to select the patients?

No, we didn’t. So it was a study in all comers but we looked very carefully at potential values of predictive biomarkers.

What overall results did you get?

Well, first of all overall results were as the data have become more mature now than in the interim analysis now this has become a phase II randomised positive clinical study, meaning the overall survival with atezolizumab immunotherapy in relapsed non-small cell lung cancer was significantly better than with our current standard, docetaxel chemotherapy, hazard ratio 0.73 and a significant p value. So that’s one of the primary endpoints that is met.

That’s a big overall improvement for all the patients but what about those with the biomarker, the PD-L1?

Yes, the biomarker for that type of treatment which is really revolutionising the whole cancer treatment field, my feeling is that biomarkers will be very important because some patients do not have any benefit from that treatment while other patients have really long-term benefits, several years that they remain in good condition, with a treatment that is on average well tolerated. So it’s important to distinguish these populations, the ones with the long-term benefit, the ones without any benefit. It’s not so easy, PD-L1 immunohistochemistry has been the proposed test at the present time but it’s not so very refined. So what we did in POPLAR we did not only look for the immunohistochemistry for the biomarker on the tumour cell but also in the environment, the immune environment, on the tumour cell. This has, as a consequence, it’s a bit more complex, the way you look at the staining is a bit more complex, but perhaps that’s not so bad because the interaction between the immune system and the cancer cell is probably very complex either. So I think this biomarker could be a step up from what we had until now, just staining PD-L1 on tumour cells.

You’ve got tumour cells but you’ve also got infiltrating cells.

Yes, immune cells. Yes.

Immune cells, yes. If the expression is positive on both how much of an improvement in efficacy does that mean?

So what we have documented, and it’s a phase II randomised controlled trial so it’s almost 300 patients, but in that context it’s not much. What we have seen is that the stronger the biomarker is the stronger the effect on overall survival advantage compared to docetaxel chemotherapy was. So it was really a clear relationship – the stronger the biomarker the more benefit the patient had. Again, this is a study so when you go to subgroups, it’s a study of 300 patients, I don’t think it’s a real fact, it’s significant, in some groups it’s no longer significant sometimes because you go to lower numbers. What is important is that there is an ongoing study, OAK, exactly the same design, the same patients, the same trial setting, and that study will have more than 1,000 patients looking at exactly the same characteristics. If this is confirmed, and I think it will be confirmed, it’s a major breakthrough in predictive biomarkers for immunotherapy.

So it doesn’t change therapy yet but it might?

It doesn’t’ change therapy yet but it might. There are immunotherapies already registered and in clinical practice but we still struggle with biomarkers, clearly. So if this is succeeding in the larger phase III trial it means we will have an immunotherapy with a solid biomarker which is clearly to be preferred because you then give the drug, which is expensive, to the patients who really need it and you spare it from patients who don’t really need it.

So how would you sum up the clinical relevance of this to busy cancer doctors or the potential relevance?

The clinical relevance is that for the treatment of relapsed non-small cell lung cancer immunotherapy with atezolizumab offers a better efficacy in terms of overall survival than the current standard. It is far better tolerated in terms of side effects, the severe side effects with docetaxel are not minor. Here we have only 11% and most of them were even not treatment related. And the hope is and the signals are that we probably will have a good predictive biomarker for that type of treatment.

Thank you very much.

You’re welcome.