ASCO 2015

PM1183 plus doxorubicin shows interesting activity in small cell lung cancer

Dr Emiliano Calvo - START Madrid, Madrid, Spain

The studies are a combination, a study of two drugs, PM1183 with doxorubicin and actually it’s a part of a phase I study, it’s the expansion cohort, to evaluate the activity and tolerance profile in a cohort of patients with advanced small cell lung cancer in progression to first line therapy.

What are the findings of your study?

I think that the most striking finding, the most significant one, is the high rate of responses, objective responses that have been seen in this difficult to treat population which is actually an unmet need. Out of the 21 patients that were in this expansion cohort we saw 65% of responses, two out of three patients were having an objective response with a 95% confidence interval from 45% to 85%. We have to remember that doxorubicin by itself or in VAC combinations only provides the patients with 25%, 20% of responses. So it is quite a significant, relevant response rate and this occurs, not only for patients with sensitive disease to carboplatin or to previous platin but also we see that one third of the patients with platin-resistant small cell lung cancer are also achieving an objective response.

There was some toxicity shown, could you elaborate on this?

Yes, the tolerance profile actually is a good one. The main toxicity or the one that we see more frequently is a neutropenia but it is a predictable neutropenia and easy to manage. Sometimes this implies or involves some dose delay more than dose reduction but it is not of severity as to have the patients with treatment for their health.

What are the clinical implications?

Yes. I think these findings are very important in the sense that small cell lung cancer is one of the very few tumour types that in the last decade we didn’t find anything new. Actually there is not a clear standard in second line therapy at the progression to platin etoposide. So this very high response rate with also very acceptable prolongation of progression free time of four or five months is giving us some hope in the sense that we have to test this in a randomised phase III trial to see if these interesting numbers remain the same in a larger population and comparing to the standard.

What is the take-home message for cancer doctors?

The combination of PM1183, which is a DNA transcription inhibitor, plus doxorubicin seems to be preliminary active and synergistic with an acceptable tolerance profile.