The IMforte trial was a global open-label randomised phase III study that investigated the efficacy and safety of lurbinectedin in combination with atezolizumab as compared to atezolizumab alone for the maintenance treatment of those patients with extensive stage small cell lung cancer whose disease did not progress after third-line induction treatment with atezolizumab plus carboplatin plus etoposide. So, in summary, it was the study evaluating the role of the combination of lurbinectedin plus atezolizumab as first-line maintenance treatment for extensive stage small cell lung cancer.
What were the results of this study?
In this randomised trial it was a clinically relevant improvement that, of course, was also statistically significant in terms of PFS for those patients treated with the combination of lurbinectedin plus atezolizumab as compared to atezolizumab alone with a hazard ratio of 0.54 and a p-value of 0.0001. That means a decrease in the risk of progression along the study period of 46%, this translates into an increase in median PFS from 2.1 months to 5.4 months and I think that’s pretty significant.
There was also a consistent increase in the other primary endpoint, overall survival, that was clinically meaningful with a hazard ratio of 0.73 and a significant p-value of 0.0174. That translated into an improvement in median OS from 10.6 months to 13.2 months in the lurbinectedin plus atezolizumab combination. I have to say here that in that trial, because it’s a maintenance study, we started to measure survival from the time of starting maintenance treatment after four courses of induction treatment. So since diagnosis already 3.2 months had already elapsed.
The other thing I have to comment in terms of results is that the safety profile of the combination was predictable, so we didn’t find any new signal. Of course there were some more side effects in those patients treated with lurbinectedin plus atezolizumab, for example, there were more grade 3 or 4 treatment-related adverse events – 26% as compared to 6% – but the treatment -related grade 5 events were very similar – 0.8% and 0.4% – and the impact in treatment discontinuation was quite low – 6.2% of the patients in the combination as compared to 3.3% of those patients treated with atezolizumab. Finally, I have to remark that there was not an increase in any immune-related side effects.
What is the clinical significance of these results?
For me, given the statistically significant but also clinically meaningful improvement in OS and PFS, and taking into account the safety profile of the combination, I think the IMforte combination of lurbinectedin plus atezolizumab has the potential to become the new standard of care for those patients with third-line maintenance therapy in this very aggressive and difficult to treat disease of extensive stage small cell lung cancer because I truly believe those patients are benefitting from this therapy.
Of course, not every single patient is going to be a candidate. For example, in this trial we didn’t include patients with brain metastasis at diagnosis, but for most of the patients where we do not foresee a contraindication it’s going to be a good alternative.
