Practice Update | Onology

Q & A 30

Critical issues in thoracic oncology Interview with Wilfried Eberhardt MD

Dr Jennifer Caudle speaks with Dr Eberhardt, from the Department of Medical Oncology at the West German Cancer Center at the University Hospital Essen, University of Duisburg-Essen, on the use of immunotherapy in the neoadjuvant setting for localised non-small cell lung cancer, and recent developments in the management of malignant pleural mesothelioma.

DrCaudle You previously reported similar out- comes for resectable stage 3 non-small-cell lung cancer tumors treated with induction chemotherapy followed by either defini- tive chemoradiotherapy or surgery in the ESPATUE trial. In light of the recent advances with immunotherapy in combination with chemotherapy seen in the KEYNOTE-021 in the metastatic setting, what are your thoughts about immunotherapy being uti- lized in the neoadjuvant or definitive setting for localized non-small-cell lung cancer? Dr Eberhardt With the studies in the recent years in locally advanced non-small-cell lung cancer stage 3, we’ve been through a time where we most optimized the local regional approach. The systemic approach was usu- ally platinum-based chemotherapy, and at the end of the day, still we find that only up to 25% to 40% of the patients are cured, so the patient relapse and die. The most impor- tant issue currently is to improve the systemic treatment in this lung cancer stage, so immu- notherapy based on the results in stage 4, is a very interesting new approach to use. In recent weeks, we’ve already heard through press release that there is a possi- bility that with consolidation immunotherapy

cisplatin/pemetrexed in the North American Guidelines. The National Cancer Center, the national guidelines also state that it is possible to give bevacizumab in mes- othelioma in combination with cisplatin/ pemetrexed. It is not so much used in Europe, but in the US you can use it, so we know that targeted agents may improve the results in some of the patients. We have seen at this conference, also, that the new immu- notherapy, the PD-1 or PD-L1 acting drugs, these are interesting drugs because we’ve seen that they work in some patients. And it is possible, probably, also to give combi- nations of chemotherapy with these new antibodies, and probably thus we can improve the systemic effect, and also by improving the systemic effect we can also have better local treatment. Dr Caudle What are some of the newer attrac- tive agents or therapeutic developments on the pipeline for treating mesothelioma? Would you say it’s some of these PD-1 or PD-L1s or are there other treatments that you’re thinking about? Dr Eberhardt At the moment, I think there is most interest in PD-1 and PD-L1 drugs and there are trials ongoing. A randomized phase 2 trial is going to be presented here at ASCO that has quite interesting results, and is probably the background for a fol- low-up phase 3 trial. So phase 3 trials we will need, but we know that patients who have a high PD-L1 expression also that they have a better response to PD-1 antibodies, for instance, or PD-L1 antibodies, and so also a patient selection could be possible, and I think this will be progress for some of the patients.

we might improve the results for some of the patients. So, we are eager to get new results on this issue, and at this confer- ence (ASCO 2017) we already have seen a phase 2 trial looking at an immunotherapy as consolidation. These results were pre- sented here in the poster discussion, and it is feasible, the toxicity is manageable, so the hope is that through using immunother- apy in these patients with stage 3 non-small cell lung cancer, the systemic relapse can be prevented in some patients. Dr Caudle Can you comment on some of the current developments in the manage- ment of malignant pleural mesothelioma, and what are your thoughts regarding the recent study showing benefit of adding of target agents to chemotherapy? Dr Eberhardt Pleural mesothelioma is still a disease with a large unmet need. We need better systemic treatments. We have the cisplatin and pemetrexed regimen, which is a standard approach, but usually the patient relapse. So we know that drugs, VEGF-acting drugs, anti-angiogenic drugs, and drugs acting on PD receptors, these are interesting drugs. I mean, there is data on bevacizumab in combination with

Upfront PD-1 inhibitor treatment for NSCLC: a new paradigm Dr Roy Herbst, Chief of Medical Oncology and the Associate Director for Translational Research at the Yale Cancer Center

in New Haven, Connecticut, discusses the impact of KEYNOTE 021 and 024 studies on the upfront management of advanced non-small cell lung cancer.

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