When Phase 3 Data Can't Guide Clinical Decision-Making in the Real-World--Lumpers vs Splitters

In a perfect world, we would have phase 3 data to guide all of our clinical recommendations. But even if that were possible, phase 3 trials are not able to provide the full range of answers we need in a real-world setting. Do, for instance, the results from a trial of the most fit patients with great organ function apply to our older and somewhat frail patient with poor kidney function?

In a world of precision oncology, oncologists face decisions every day about whether our data from idealized patients apply to the patient with a comorbidity or other complicating clinical feature. It's important to acknowledge the uncertainty when extrapolating data from even the most definitive trials.

Currently, for example, we struggle with the question of whether or not patients with unresectable stage III non–small cell lung cancer (NSCLC) harboring an EGFR mutation or ALK rearrangement should pursue consolidation durvalumab for a year. These patients were included in the PACIFIC trial, but most of what we've seen of patients with driver mutations, at least EGFR and ALK, indicates that they derive little benefit from immunotherapy. Beyond that, there is a real risk for toxicityfrom the interaction of recent immune checkpoint inhibitor therapy with a newly initiated tyrosine kinase inhibitor.