Clinical Cases in Lung Cancer - Episode 11

Case 2: EGFR+ NSCLC Combination Therapies

Mark Socinski, MD: We alluded to the RELAY trial before, which took a first-generation drug, erlotinib, again in the same population that we saw in FLAURA, added ramucirumab, in this case on an every-2-week treatment.

Another key feature of this is that brain metastases were excluded, were a key exclusion criteria. Again, the primary end point was progression-free survival. You see here the progression-free survival with a hazard ratio of 0.59, so not quite as robust as we saw with the FLAURA data. I don’t think the toxicity shown in the table is surprising to anybody given the use of an anti-VEGF agent. We saw similar results with bevacizumab from one of the Japanese trials, and you see the same effect on PFS as well as the safety in this particular setting, but no convincing benefit in overall survival. These are the data that we’ve seen from the Japanese trial and, again, from an overall survival point of view, certainly not what we saw in the FLAURA trial with the survival advantage with osimertinib here.

Another interesting path is we’ve had a couple of trials that have reintroduced chemotherapy into the combination with a TKI in the EGFR mutated space. Again, this is the Japanese trial with gefitinib plus or minus chemotherapy. We did see in this trial not only a PFS, but an overall survival advantage in this population. So very interesting. Obviously, there were no surprises with regard to the adverse events adding chemotherapy back in, pretty much what we would expect. Of course, if you go back, way back, I can’t even remember—Ed, maybe you’ll remember—but all the trials in unselected populations where we added gefitinib to chemotherapy or erlotinib to chemotherapy, all of which were negative in unselected populations, there was no concern about giving the TKI with chemotherapy from a toxicity point of view, and I think these data bear it out.

Transcript edited for clarity.