Today I presented the results of our post-hoc analysis of the CASPIAN trial looking at the relevance of laterality in small cell lung cancer. The CASPIAN trial was a phase III trial evaluating the role of chemoimmunotherapy in untreated patients with extensive-stage small cell lung cancer. The results of this trial clearly established a new standard of care for this group of patients, confirming the role of chemo/IO with platinum, etoposide and durvalumab as the standard frontline setting.

In this post-hoc analysis we looked at the impact on survival according to the laterality of primary tumours. In particular we tried to confirm the results of another retrospective trial, the ALBA study. The ALBA study was a retrospective study done at three centres, two in Italy and the other one in Munich, Germany, in which we analysed the survival outcomes of more than 200 patients. We found that patients having their primary lung lesion in the right left a longer survival. In this analysis in the CASPIAN trial we confirmed our previous results, so patients having primary lung tumours in the right side had longer survival.

We also analysed the biological rationale, the biological background, supporting these findings and we observed that those tumours in the right side had a different biological profile compared to tumours located in the left. Particularly in left tumours, we found less CD8 infiltration compared to the tumours located in the right side. Also when we analysed the transcriptomic profile of these tumours we observed a trend favouring a higher number of inflamed tumours in the right side.

We also evaluated the molecular portrait of the disease and, again, we observed differences between the two tumours. So patients with tumours located in the right side had a higher incidence of RB1 mutations compared to those patients having tumours in the left side. When we look at the other most common alterations, the TP53 mutations, we observed that in the left side there is a higher number of TP53 wildtype tumours. So this could explain the different outcomes in terms of survival for these patients when treated with chemo/IO.

What do you think could be the clinical significance of these results?

I consider these findings particularly important because for the first time we described the relevance of laterality in small cell lung cancer. Probably in the next trial we will consider this factor, this clinical factor, as a stratification factor in order to balance the population in clinical trials.