Garon Discusses Potential Role of Immunotherapy in EGFR-Mutant Lung Cancer

Edward B. Garon, MD

Edward B. Garon, MD

There is a need for more data regarding immunotherapy options for the treatment of patients withEGFR-mutant lung cancer, with the strongest data to date coming from the phase III IMpower150 trial, explained Edward B. Garon, MD, during the 16^thAnnual Winter Lung Cancer Conference.

This trial compared 3 different arms: a control arm with carboplatin, paclitaxel, and bevacizumab (Avastin), an experimental arm where atezolizumab (Tecentriq) replaced bevacizumab in the triplet regimen, and a third arm using all 4 agents.

In theEGFR-mutant subset of patients, the quadruplet regimen demonstrated a benefit in terms of progression-free survival (PFS) and a potential advantage in overall survival (OS) compared to the other regimens.

In an interview withTargeted Oncology, Garon, director of thoracic oncology at the David Geffen School of Medicine at UCLA, discussed these data, as well as other trials investigating immunotherapeutic agents for patients withEGFR-mutant non—small cell lung cancer (NSCLC).

TARGETED ONCOLOGY:What kind of immunotherapy options do we have for patients with lung cancer who haveEGFRmutations?

Garon:I think we are at a point where we don’t have an optimal approach to immunotherapy in this population of patients. In fact, one of the things I addressed in my talk was really the dearth of data regarding this population of patients. The strongest data to date, I would argue, is from the IMpower150 study. This is a study that actually had 3 separate arms. The control arm was the E4599 regimen, carboplatin, paclitaxel, and bevacizumab. There were actually 2 study arms, 1 that just swapped out the bevacizumab for atezolizumab, and 1 that was a quadruplet that used all the drugs, carboplatin, paclitaxel, bevacizumab, and atezolizumab. That study was for patients who had completed their therapy with EGFR inhibitors.

What was shown was that the group of patients who received the quadruplet had a benefit with respect to PFS, and although the hazard ratio 95% confidence interval did cross 1, there was at least a numerical suggestion that there was an OS advantage as well in that group of patients.

Interestingly, there was not a clear benefit or at least as clear a benefit when the atezolizumab substituted for the bevacizumab, begging the question whether there was something particular about the 4 drugs together. That, to date, I think is the most compelling data set. It is not part of the approval for this quadruplet regimen, but it is something that we are often able to get to patients based on recommendations from the National Comprehensive Cancer Network.

TARGETED ONCOLOGY:Are there concerns of toxicities with a 4-drug regimen like that?

Garon:There certainly are concerns of toxicities. If one looks at the IMpower150 study, as one would expect, the toxicity is a little bit worse with the quadruplet than it would be with the triplet, as is to be expected. The other issue in all reality from toxicity is that the backbone of the regimen, paclitaxel, carboplatin, and bevacizumab, although a very reasonable and approved regimen for many years now, has sort of lost favor among many practitioners for carboplatin and pemetrexed. It’s hard to find in the objective data what the reason for that is. When they’ve been compared with respect to efficacy, the outcomes are not particularly disparate, but when you talk to practitioners, they will tell you that it is really for tolerability. As part of the PointBreak study, tolerability was assessed and one of the things that was interesting there is that neuropathy was the one toxicity that was clearly different between the two. The other issue, which is, quite frankly, a big issue in my practice, is the hair loss. Many of my patients are continuing to work, and they don’t want to lose their hair. Also, losing your hair is something that is sort of associated in people’s minds with being sick. They don’t like that, so that’s been another issue there.

TARGETED ONCOLOGY:Where do you see this potentially having a role?

Garon:For right now, the thought would be to have this after the completion of an EGFR TKI. The data supporting PD-1/PD-L1 inhibitors prior to EGFR TKIs is quite scant. That’s where I would foresee it.

One thing I would also argue is that I’m hopeful this is not the sort of best it gets for immunotherapy inEGFR-mutant NSCLC. I think that the toxicity is significant with this regimen, and the efficacy, although in the study it certainly looked better than chemotherapy alone, we still hope for better. Hopefully we will see that in the coming years.

TARGETED ONCOLOGY:Could you also discuss the recent data for immunotherapy in unresectable stage III NSCLC?

Garon:It’s really only 1 study, but that 1 study has now led to 2New England Journal of Medicine