New Paradigms for Treatment of Locally Advanced NSCLC - Episode 4

Locally Advanced NSCLC: Treatment Overview


Mark Kris, MD: Let’s talk about the management of the different local modalities. Again, I’m going to be the thoracic surgeon, here. Our ability to evaluate, stage, and, ultimately, resect has improved tremendously. I’m shocked, as an observer, to see people who have a thoracic surgery spend 1 night in the hospital and take no analgesics. It’s just extraordinary. Again, that’s not the case for every patient, but they can do that now. The whole metric on the invasiveness of surgery has changed tremendously. Also, what is resectable versus not? Pneumonectomy has just about disappeared. At my institution, by doing sparing operations, by doing sleeve resections, I know that things like a pneumonectomy are pretty rare.

Other opportunities with surgery include the use of neoadjuvant and adjuvant therapy. For the rest of this discussion, we could speak on the advantages of neoadjuvant therapy. I’m a strong believer in that. In thoracic surgery training, I learned this. Literally, the thoracic surgeons at our institution are the ones who brought neoadjuvant chemotherapy to the forefront. It’s got some great, great advantages. It’s better tolerated, and the beautiful thing about it is you know whether it’s working. You can tell, often, from radiographic studies. But you can also tell from the resection specimen—at the time of surgery—and you can very carefully plan therapy with that information. So, with great opportunities in the adjuvant and neoadjuvant space, surgery is an important consideration for a lot of patients with stage 3A disease.

In stage 3B disease, I think there is consensus that there is still no clear role for thoracic surgery. But, again, please make sure that the questions on being operable and resectable are nailed. Walter, what are your thoughts on the guidelines for optimal radiation treatment for patients with stage 3 disease, who are inoperable, unresectable in 2018?

Walter J. Curran Jr., MD: We have a lot of tools available for radiation oncology management in these patients. I’ll just focus on those that really should be considered in any department or any clinic that’s really committed to those patients. We have CT-based treatment planning. We have image-guided radiation. We also have intensity-modulated radiation. Every patient should have those tools available to them. The physicians may or may not always need to use them. Image guidance really allows a radiation oncologist to look at a patient whose target moves fairly significantly in the respiratory cycle, perhaps because the person just struggles with breathing, in a quiet way, on a table, or due to other confounding factors. Historically, radiation oncologists would give large margins above and below the tumor. That would put the patient at risk for too low of a dose of radiation or too high of a risk for radiation-related pneumonitis.

Now, we cycle our treatment delivery with the various phases of target motion. While that may seem to be technically simple, it actually ends up requiring some fairly sophisticated hardware and software. But it is well worth the effort. Intensity modulation allows for some creative ways, to go beyond just treating a tumor from the front and the back, or from one angle or another. It really allows us to take into account the full 3-, if not 4-dimensional contour of the target—the normal structures. So, you can actually give the dose where the tumor is and reduce the dose to structures that don’t need radiation, such as the heart, the spinal cord, and the normal lung.

The Radiation Therapy Oncology Group provided a very thought-provoking trial. We saw a reasonable radiation dose escalation associated with poorer survival over a standard dose. And when we studied the results, we actually determined that it might be due to too high of a dose to the heart. Those patients who had either image guidance or intensity-modulated radiation did not have that high of a dose to the heart. The tools are not always used, in every clinic, to the same degree in which they had used them. You really do need a committed team of radiation oncologists, physicists, and therapists to really execute this work.

Now, there’s also a lot of excitement about stereotactic radiation, which usually involves a much higher single dose of radiation that is delivered 1, 2, 3, or 4 times, rather than over a 6-week course. Most of the progress in lung cancer with stereotactic radiation has been for smaller tumors, not for stage 3 disease. But, now there are trials. We have one, at Emory University, where we’re using the stereotactic treatment as a boost dose to a “calmed down” volume. I think we’ll see that, more and more.

The final area in radiation that’s quite interesting is proton therapy. Proton therapy has demonstrated the ability to reduce normal tissue dose even better than intensity-modulated radiation, in some patients. Right now, at NRG Oncology, we have an NCI-sponsored trial that compares intensity-modulated radiation to proton therapy, with all patients receiving concurrent chemotherapy.

Mark Kris, MD: Jyoti, could you say a word about the other component of this bi-modality therapy—chemotherapy? What drugs are used? Do you have go-to drugs? What are the pros and cons of the different drugs?

Jyoti D. Patel, MD: Absolutely. There are multiple chemotherapy backbones that are very reasonable to use. Probably, the most accepted, based on phase III data, is cisplatin and etoposide. That can be challenging for some folks—getting 5 days of chemotherapy. But, it’s during radiation. So, that time overlaps. A large number of American oncologists primarily treat with carboplatin and paclitaxel, based on familiarity with these drugs. This is done weekly. Traditionally, people who use carboplatin and paclitaxel also give a consolidation afterward, with 2 cycles—sort of a full dose. And then, more and more, we’re seeing a lot of cisplatin and pemetrexed, based on the PROCLAIM data. Although it was essentially a negative study, it basically showed noninferiority with equivalence.

I think all of these options are very reasonable. Most depend on patient and oncologist preferences. Cisplatin/pemetrexed isn’t associated with alopecia, for example. That’s just great. It’s 1 treatment, every 3 weeks. The carboplatin and paclitaxel regimen has been widely adapted because of toxicity. I think it’s a little bit better. It’s more well tolerated.

Mark Kris, MD: I’m going to put you on the spot. What is your go-to regimen for a patient with adenocarcinoma, who’s fit?

Jyoti D. Patel, MD: You know, it’s really evolved. Certainly, I’ve been using a lot of carboplatin and paclitaxel because that was the best choice based on data from the study that Walter was talking about. That set a new standard. It shifted my practice, in adopting it over the past year or 2. But now, with the integration of immunotherapy, I think I might be giving more cisplatin/pemetrexed again.

Mark Kris, MD: And, for a patient with squamous cell cancer?

Jyoti D. Patel, MD: Again, I primarily give carboplatin and paclitaxel. But I may evolve to use cisplatin/etoposide.

Mark Kris, MD: I have to say, I have never been a fan of etoposide because of its lack of single-agent activity. I know it has been thrown into a lot of regimens. I generally prefer to give 2 active drugs. Cisplatin would be my go-to drug. I may use pemetrexed in the case of adenocarcinomas. And I’d probably give a taxane. Docetaxel—we’ve had a lot of use with that. But you could easily use paclitaxel or albumin-bound paclitaxel for many reasons.

Transcript Edited for Clarity