Anti–PD-L1 atezolizumab or chemotherapy as second-line therapy in patients with SCLC

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Published: 26 Oct 2018
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Prof Jean-Louis Pujol - CHRU de Montpellier, Hôpital Arnaud de Villeneuve, Montpellier, France

Prof Jean-Louis Pujol peaks with ecancer at ESMO 2018 in Munich about the study into the use of anti–PD-L1 atezolizumab or chemotherapy as second-line therapy in patients with small cell lung cancer.

Prof Pujol explains that they found that only 1 patient out of 49 in the atezolizumab group had a response at 6 weeks.

He states that the progression-free survival differed significantly in the two groups in favour of the chemotherapy, and the difference in overall survival was not tangible.

For more in SCLC, Dr Noemi Reguart gave her conference highlights here.

ecancer's filming has been kindly supported by MSD through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

This is a phase II randomised non-comparative study that aimed at determining whether or not atezolizumab will be a candidate for second line treatment in small cell lung cancer with recurrent disease after first line conventional chemotherapy, namely carboplatin etoposide. In fact we have a randomised study, two to one, between atezolizumab and chemotherapy but we left the chemotherapy free so this is investigator’s choice to decide whether they prefer to give at induction carboplatin etoposide or topotecan. The primary endpoint was the overall survival at six weeks in the eligible patients in the atezolizumab group, of course. We also have secondary endpoints, namely safety, survival and also quality of life and markers.

I’ll go directly to the results because it’s what is important to say here in the short time of this interview. In fact, we have only one patient out of 49 in the atezolizumab group who presented with a response at six weeks. That gives a 2.3% overall response rate and when we add patients with disease control we have a disease control rate a little higher, about 9.5%. We also analysed, of course, the safety and we have no safety signal, very unknown. We have some adverse immune events such as musculoskeletal and connective tissue disorders, gastrointestinal disorders, but anyway there is no grade 3 significant safety signal.

Survival, the progression free survival differed significantly between the two groups in favour of the chemotherapy. That is to say that in the atezolizumab group we have 1.4 months PFS and the hazard ratio for the atezolizumab arm was 2.26 so it’s favourable for chemotherapy. But when we look at the overall survival the overall survival in the atezolizumab group was 11.4 months and in the chemotherapy group it was 9.5 months. The difference is not significant. The quality of life improved in both groups in parallel, we have nothing to say about that.

Finally, about the markers we tested three different things. First we tested the PD-L1 expression of the tumoural cells but there is only one patient with an expression of PD-L1 on tumour cells, that is to say this is only a 2% frequency so it’s not possible to make any subgroup analysis. But when we look at the immune and free treating cells we have a little bit more with 16 tumours that were positive but that doesn’t identify a specific subgroup that could benefit the most from atezolizumab.

Finally we are undergoing a next generation sequencing of DNA fraction on free DNA, circulating free DNA, and on tissue DNA. For the moment what I can say is that most of the patients presented with mutations, that p53 and RB1 alterations are almost ubiquitous and we try to find the genes that could identify a subpopulation that could benefit from the atezolizumab.