According to Jason Porter, M.D., a medical oncologist and hematologist at the Western Cancer Center and Institute in Memphis, Tennessee, it’s important to have a multidisciplinary approach to treating patients with small cell lung cancer. This team approach allows early intervention for signs of recurrence or progression, Porter said in this interview. American Journal of Managed Care® (AJMCMore®).
For the future of small-cell therapy, Porter hopes that there will be options for more targeted therapeutic approaches. He also hopes that small cell therapy will catch up with non-small cell lung cancer through subtyping.
AJMC: What is the approach for monitoring patients for possible recurrence?
Porter: This is a very voracious tumor. It grows fast and needs a lot of nutrients. The reason chemotherapy is so effective is that it can penetrate DNA and actually stop DNA replication when cells are trying to build it. Therefore, they take it up faster than normal cells and react and die faster than normal cells. Unfortunately, in most cases, resistance mechanisms exist, after which those cancers develop resistance and grow.
How a patient is investigated depends on the patient’s clinical presentation. If there is brain involvement at the time of presentation, we plan to treat her with whole-brain irradiation or gamma knife and closely follow her MRI of the brain. Imaging of the brain is repeated when new neurologic symptoms develop. Even if you do not have brain disease at diagnosis, you are very likely to develop brain disease or metastatic disease to the brain if you live long enough. Brain imaging studies are performed approximately every 3 to 6 months. Otherwise, during initial treatment he will have a CT scan and scans every 2 cycles, so I will check almost every 6-7 weeks. Once the patient is stable, he will probably have scans every three months. I keep the scan intervals between him no more than 3 months, from his 9 weeks to his 12 weeks, which is a more stable part of the course of the disease.
AJMC: What are the factors to consider when choosing a treatment for a patient who has relapsed after first-line small cell lung cancer?
Porter: Initial first-line treatment will be platinum doublet chemotherapy with an immune checkpoint inhibitor. We base treatment on a patient’s ability to tolerate treatment and their willingness and consent to tolerate treatment or to receive chemotherapy because some patients do not want it. After starting, what happens on the second line depends on what happened on the front line. If I have had a long-term response to initial treatment, for example, if I continue chemotherapy and have been on immune checkpoint inhibitors for 6 months to 1 year before relapse, I may be re-challenged with a platinum doublet. is expensive. Lurubinectedin is currently approved as a second-line drug for advanced extensive-stage small cell lung cancer and has been shown to have some impact on time to recurrence. Within 3 months, you are less likely to re-challenge platinum and more likely to progress to the new mechanism of action of lurubinectedin. If 6 months have passed, it must be determined whether the prior platinum doublet chemotherapy caused significant toxicity. If so, I am unlikely to try them again. However, if not, you may retry for Platinum after 6 months. If side effects such as peripheral neuropathy or renal failure from the platinum doublet do occur, I would be less likely and more likely to try lurubinectedin. Irinotecan and topotecan are certainly options, but they can be a little more difficult from a scheduling standpoint. These patients have advanced and aggressive small cell lung cancer. For topotecan, treatment should be within 5 consecutive days. Lurubinectedin, on the other hand, is one day out of a 21-day cycle, which is very convenient for patients with very inconvenient conditions.
AJMC: There have been recent updates to the NCCN Guidelines. Are topotecan and lurubinectedin still useful, or is it really a patient-by-patient decision whether or not to use these particular treatments?
Porter: I think it depends on the patient. To be honest, I don’t use topotecan. You have other options. I would probably use a platinum doublet weekly before giving topotecan. In the 6-month setting, when looking at the lurbinectedin data from pivotal trials, phase 2 trials with lurbinectedin showed very long chemotherapy-free intervals of 100 days or 180 days, or 6 months. I indicated that I had a patient. Response to lurubinectedin. 11.3 months. If you give a single drug in that setting and you get an 11-month response or overall survival, that’s actually very good. I keep telling myself that the chemo-free period and the platinum-free period should really be separated, they are not the same. Therefore, an additional 11 months of rubinectedin and the ability to take platinum long term would be a precursor to an even higher platinum sensitivity for me. Even platinum re-challenges are more likely to come back after lurubinectedin. On line 3, if the patient is still doing well enough, we’ll probably give them a platinum re-challenge. If they react to platinum again, they can react for a very long time. Another thing to say is that certain patients were able to stay on small cell therapy for more than a year, so their disease may be slightly less progressive than those who didn’t get 180 days of chemotherapy. It means that there is sexuality. free spacing. In these patients the disease biology itself has already been defined.
AJMC: What strategies are you adopting to optimize the patient’s quality of life in the management of small cell lung cancer?
Porter: Focus on the patient’s symptoms, ensure palliative care is part of the treatment process, and plan to address what’s important to the patient, such as managing pain and shortness of breath. I have assembled a multidisciplinary team to ensure that small cell patients at high risk of chronic obstructive pulmonary disease (COPD) are referred to pulmonologists for appropriate inhalers and bronchodilators. to This is very important because they are short of breath because they are on immune checkpoint inhibitors and we don’t know if it’s pneumonia or just her COPD getting worse.
We should use multidisciplinary care for these patients. I believe that the more eyes we monitor, the more often healthcare providers will come into contact with us, and the sooner we can intervene if there are early signs of disease recurrence or progression. In small cells, it occurs so quickly that the patient may soon be no longer a candidate for further treatment. Maintaining collaboration and working together as a team is critical to the care of these patients.
For them to be aware of their disease status and to be very transparent with them. For example, this has progressed in just 3 months of treatment, but we are still platinum, we are already growing and we want the patient to understand that this is not optimal. As they move on to the next treatment that they may actually tolerate, they are already thinking about what they need to do from a family perspective or a higher order perspective, and what they will do if they don’t survive the disease. making plans. We don’t want it to come as a surprise to patients. To help them make decisions, the more information we give them, the better decisions they can make.
AJMC: Can you tell us what you are working on with small cell lung cancer?
Porter: I think the biggest problem with small cell lung cancer today is how to maintain the initial response. One thing I’m really looking forward to is an ongoing clinical trial investigating a platinum doublet in combination with an immune checkpoint inhibitor as induction therapy, followed by maintenance therapy with an immune checkpoint inhibitor in combination with lurubinectedin. . Will all patients respond? Some patients have a prior response, but we do not know whether it is an immunotherapy response or a chemotherapy response. We see how high response rates were before immunotherapy became part of the treatment paradigm for small cell lung cancer. This is indeed the end of the curve and survival from the Caspian and his IMpower133 trials, with long-term survival seen. It is most likely due to immune checkpoint inhibitors. We have patients who are dependent on chemotherapy. I think lurubinectin as maintenance is really interesting. I can’t wait to see what happens there.
Also, from the second line onwards, clinical trials have recently been conducted, but no patients have occurred to date. The PIN 866 molecule explores the irinotecan metabolites, which are essentially related to the delivery mechanism, by directing the irinotecan metabolites into small cells and delivering them there in a more targeted manner, thus limiting side effects. molecule. It is seen with irinotecan and topotecan-like drugs such as diarrhea. This targeted approach in several of my patients has been tested for a year and has had few side effects. It’s a way of managing the disease using the medicines we normally use, but in a more targeted way that limits side effects. These are some of the things that are going on right now.
Finally, another thing is that not all small cells are the same. There are various subtypes. Using subtypes would allow us to re-target different variations of small cells, just as we do in non-small cell lung cancer. I’m not actively involved in subtyping research, but I’m watching closely. I look forward to the day when small cells can actually be subtyped in the same way as non-small cells.