Personal Approach in Treatment Compared to Clinical Trials

Vivek Subbiah, MD: Distilling from all these trials, what is your personal approach to treatment in a newly diagnosed patient that presents to your clinic? Let’s take it from Dr Ganti first.

Apar Ganti, MD: There are a lot of things to consider than starting patients on treatment. One of the important things I have encountered in practice from a logistics standpoint is a lot of these patients may have to start treatment in the hospital, and there are some logistical issues with getting the checkpoint inhibitors while the patient is in the hospital. Oftentimes we have to start them with platinum/etoposide, get the first cycle in the hospital, and then once they are in the outpatient setting, add the check point inhibitor afterward.

As far as deciding which check point inhibitor to use, the 1 striking thing I’ve found from the IMpower133 and CASPIAN studies is that even though there were some slight differences in the inclusion and exclusion criteria—as Dr Chiang mentioned, asymptomatic brain metastases were allowed in the CASPIAN study—it is striking how similar those results are, suggesting that this benefit with check point inhibitors is real benefit. Oftentimes you see when you have different studies that some show more benefit compared with the others, but if you look at all 4 of these trials that we’ve talked about and forget the statistical significance part of it, if you look at the magnitude of benefit—the difference in benefit, the absolute overall numbers—they are so strikingly similar to one another, suggesting that this is a real benefit. Based on that, I would suggest that all these patients be treated with a check point inhibitor in the first-line setting. My personal preference has to do with where I live and the distances people have to travel to come visit me. If you look at IMpower133, it was an every-3-week regimen, with the maintenance given every 3 weeks. The CASPIAN study was chemotherapy given every 3 weeks, with maintenance given every 4. I have had patients tell me that they would do whatever if they can make fewer trips. For patients who come to me from 3, 4 hours away, I tend to use durvalumab, whereas with patients who live close by and don’t have problems making the trip, either option would be fairly reasonable.

Vivek Subbiah, MD: Thank you so much, Dr Ganti. Let’s turn to Dr Chiang. Dr Chiang, which regimen are you using in your own patients, and does your clinical experience match with what was seen in the clinical trials that we just saw?

Anne Chiang, MD, PhD: Yeah. The fact that both IMpower133 and the CASPIAN trial showed very similar overall survival provides good options, validation No. 1, and good options for our patients. Both of them are good drugs. Within the non–small-cell space, we’ve had experience using both drugs. Atezolizumab is very well tolerated, and durvalumab we’ve used for consolidation for stage III non–small-cell, also well tolerated. I will say that with the COVID-19 (coronavirus disease 2019) in this era, we did look at converting our atezolizumab from every-3-week to every-4-week administration. For durvalumab, we also considered doing it every 6 weeks just to keep people out of the office and out of the health care system if we could. For patients with asymptomatic brain metastases, I would prefer durvalumab.

I agree with Dr Ganti that many of these patients are sick and started out in the hospital. We can’t start the immunotherapy in house, so we end up starting it afterward. Are they interchangeable? I don’t think we have information that says that 1 is clearly different from the other. Aside from the brain metastases issue, we could probably use either 1. I have used both. Additionally, we used the atezolizumab that had FDA approval sooner, but now I have been using durvalumab as well. I would just mention that 1 issue that constantly comes up in our tumor board is if the patient has persistent disease, do you consider thoracic consolidation? A fight we have every week is between the radiation oncologists and the medical oncologists. The radiation oncologists say, “Gee, it’s certainly tolerated well with immuno-oncology and the radiation, and we think we can have a better benefit.” But clearly, the trials did not include thoracic consolidation, so if you’re a purist, you really try to follow the data. For me, unless there’s a clear reason to use radiation—for example, if the patient is symptomatic and there is a need for some local effect—then I hold off on that, but I know that’s a bone of contention. I don’t know what you guys do.

Apar Ganti, MD: I agree. That has been a challenge. What I tend to do is, if someone has had good response outside the chest and has a less severe disease within the chest—of course, we don’t know if this is inflammation with that tumor tissue—I at least talk to the patient about possibly considering thoracic radiation. I understand that neither of the trials allowed it, so it is a data-free zone if you will, but given what we know about the benefits of thoracic radiation and the kinds of people it will benefit, I would tend to offer that small portion of patients thoracic radiation. If I see a good response in the thorax, more than 90% shrinkage and good disease response outside the chest, then I’m not so sure those individuals necessarily need added radiation to the immunotherapy. I agree that we’ve done radiation with immunotherapy in multiple other diseases, and the combination seems to be well tolerated. We’ve not had too many adverse effects in that setting, so I don’t have any problems with that, but given that these trials did not include them, I would not offer it in everyone, just a select portion of patients for whom I think adding the radiation would help improve the quality of their response.

Transcript Edited for Clarity