Dr Jason Porter: Focus on Patient-Centered Care in the Treatment of Small Cell Lung Cancer

It is important to have a multidisciplinary approach in the treatment of patients with small cell lung cancer, according to Jason Porter, MD, medical oncologist and hematologist, West Cancer Center and Research Institute, Memphis, Tennessee. This team approach allows for early intervention with signs of relapse or progression, Porter said in this interview with The American Journal of Managed Care^® (AJMC^®).

For the future of small cell treatment, Porter hopes there will be options for more targeted approaches to treatment. He also hopes that small cell therapy will catch up with non–small cell lung cancer with subtyping.

AJMC: What is your approach to monitoring patients for potential relapse?

Porter: This is a very greedy tumor. They grow fast so they need a lot of nutrients. The reason that the chemotherapies are so effective is because when they are trying to build DNA in those cells this chemotherapy can get intercalated into the DNA and it actually will stop DNA replication. So, they take it up faster than our normal cells, and they respond and die faster than normal cells. Unfortunately, there is going to be a resistance mechanism most times, and then those cancers will become resistant and grow on.

The way I survey patients depends on their clinical presentation. If they have brain involvement at presentation then I am going to treat that with whole brain radiation or gamma knife and then follow MRIs of the brain very closely. Any new neurologic symptom is going to prompt repeat imaging of the brain. If they don't have brain disease at diagnosis, if they live long enough, there is a very high likelihood that they will develop brain disease or metastatic disease to the brain. I will survey them about every 3 to 6 months with brain imaging, and otherwise CT scans at initial therapy, I will scan after every 2 cycles, so every 6 to 7 weeks pretty much. After patients are stable, I will go on to maybe scan every 3 months or so. I don't let my scanning intervals go beyond 3 months, so I keep it between 9 and 12 weeks at the more stable portion of the disease process.

AJMC: What are some of the factors that you consider when selecting a regimen for these patients who have relapsed following the primary therapy in small cell lung cancer?

Porter: Initially, the primary therapy is going to be a platinum doublet chemotherapy with an immune checkpoint inhibitor. We go on to that based on the patient's ability to tolerate therapy and also their willingness and agreement to tolerate therapy, or to take chemotherapy because some patients don't want it. After we start, what happens in the second line really depends on what happened up front. If they responded for a long time with their initial therapy, for example, they went on their chemotherapy and were on maintenance immune checkpoint inhibitor for 6 months to a year before they relapsed, then I'm likely to rechallenge with a platinum doublet. We do also know that now lurbinectedin is approved in second line for extensive-stage small cell lung cancer that progresses, and there is some implication in how long it is before they relapse. If it has been 3 months or less, then I am less likely to rechallenge them with a platinum and much more likely to go on to a new mechanism of action with the lurbinectedin. If it has been 6 months then I have to decide, did they develop significant toxicity from their platinum doublet chemotherapy upfront? If so, I am unlikely to rechallenge them. But, if not, then I may rechallenge with platinum at 6 months and beyond. If they did develop side effects like peripheral neuropathy, renal failure from the platinum doublet, then I am less likely and more likely to challenge with lurbinectedin. Irinotecan and topotecan are options for sure, but can be a little bit more challenging from the scheduling perspective. These patients have progressive and aggressive small cell lung cancer. With topotecan, they would need to come in 5 consecutive days for treatment. Whereas, with lurbinectedin, it's 1 day out of a 21-day cycle so that's a lot more convenient for those patients in a really inconvenient circumstance.

AJMC: There was a recent NCCN guideline update. Do you still find usefulness for topotecan and lurbinectedin? Or, is it really on a patient-to-patient basis that you're choosing to use these particular therapies?

Porter: I think it's on a patient-to-patient basis. To be honest, I don't use topotecan. We have other options. I would probably use a weekly platinum doublet before I give topotecan. At the 6-month setting, if we look at the data from lurbinectedin from the pivotal trials, a phase 2 trial with lurbinectedin showed that patients who got to 100 or to 180 days or 6 months of chemotherapy-free interval actually have a really long response to lurbinectedin. It is 11.3 months. If you can give a single agent in that setting and get 11 months of response or overall survival, then that's actually really good. What I tell myself is, and I think that we are making a difference, that chemotherapy-free interval and the platinum-free interval really should be segregated, and they are not the same. So if I can give 11 more months of lurbinectedin and spare platinum for a long time, to me that is just going to portend an even higher platinum sensitivity. I am more likely to come back after lurbinectedin even with the platinum rechallenge. In the third line, if the patient is still doing well enough, I will probably give a platinum rechallenge then. If they respond to platinum again they are likely to respond for a very long time. The other thing that that tells us is that we were able to get beyond a year with small cell for any particular patient so that disease may be a little bit less aggressive than the patient who was not able to get to the 180-day chemotherapy-free interval. The disease biology itself is already defined in these patients.

AJMC: What are some of the strategies that you use to optimize patient quality of life when it comes to managing small cell lung cancer?

Porter: Focusing on their symptoms, making sure that palliative care is involved in their treatment process, and planning so that we do address the things that are important to the patients like addressing pain and shortness of breath. I keep a multidisciplinary team and make sure my patients with small cell who are likely going to have chronic obstructive pulmonary disease (COPD) are also seeing a pulmonologist so that they are on the right inhalers and bronchodilators. It is very important because they are getting immune checkpoint inhibitors and they are having shortness of breath, and we don't know if it's pneumonitis or if it's just a COPD exacerbation.

We have to use multidisciplinary care for these patients. I think the more eyes that are watching, the more frequently they are touched by the health care providers, then we can intervene early when there may be early signs of relapse or progression of disease. In small cell, it happens so fast that your patient can quickly not be a candidate for further therapy. Keeping a lot of hands involved and making sure that we work together as a team to take care of these patients is very important.

Acknowledging and being very transparent with them with where they are in their disease. For example, this has progressed in just 3 months of therapy and you're still on your platinum and it's already growing, this is not optimal, and making sure they understand that. As we are going on to the next line of therapy where they may actually be resistant, they are already thinking about what they may need to do from their family perspective or advanced directive perspective, and making plans in case they do not survive the disease. You want that to not be a surprise for the patients. The more information we give them to help them make their decisions the better.

AJMC: Can you tell me what you are working on in small cell lung cancer that you're excited to share?

Porter: In small cell lung cancer right now, I think the biggest question is how do we maintain the initial response? One of the things I am really excited about is the ongoing clinical trial that looks at the platinum doublet plus immune checkpoint inhibitor as the induction therapy followed by maintenance with the immune checkpoint inhibitor plus lurbinectedin. Are all patients going to respond? Some patients, we see a response upfront and we don't know if it's an immune therapy response or a chemotherapy response. We know how high the response rate was before immunotherapy was even a part of the treatment paradigm for small cell lung cancer. It is really the tail of the curve and survival from the Caspian and the IMpower133 trial where we see long survival. That is coming from the immune checkpoint inhibitor most likely. We have patients who are going to be dependent on chemotherapy; I think the lurbinectedin as a maintenance is really exciting. I am excited to see what is going to happen there.

Also, in the second line and beyond we recently had a clinical trial that is now no longer accruing patients. A PIN 866 molecule that looked at basically an irinotecan metabolite that was connected to a delivery mechanism, a small molecule that will take the irinotecan metabolite directly to the small cells and deliver it there in a more targeted fashion so that we can limit the side effects that we see with irinotecan and topotecan-like drugs like the diarrhea. That targeted approach for a few of my patients, they were on the trial for a year with very few side effects. Ways to manage the disease with drugs that we typically use, but in a more targeted manner so that we limit side effects. These are some of the things that are ongoing right now.

Lastly, the other thing is to say that all small cell is not the same. There are different subtypes. With subtyping, we will be able to target the different variations of small cell again in a way that we do in non–small cell lung cancer. I am not actively participating in the research for subtyping, but I am following it very closely. I look forward to the day where we will be able to actually subtype small cell in a way that we do with non–small cell.