As part of a Around practice: institutional knowledge Program hosted by Cancernetwork®An expert group from the University of Maryland Marlene and Stewart Greenbaum Comprehensive Cancer Center in Baltimore discussed the treatment of treatment of patients with small cell lung cancer in the extensive stage (ESCLC). The committee identified Tarlatamab-Dlle (IMDELLTRA) as one of interest, especially because of its DLL3 stargeting nature. They also discussed unwanted effects (AES) that result from Tarlatamab treatment, such as:
The committee was led by Samuel Rosner, MDan assistant professor for medicine. He was accompanied by Ranee Mehra, MDThe director of head and traps in the Department of Hematology and Oncology, Head of the Solid Tumor Department, Interim Associate Director of Clinical Research and Professor of Medicine; Michelle Sittig, Rn, Ocna nurse coordinator at the Thoracic Oncology Team; And Kaitlyn Whyman, DNP, CRNP, AGACNP-BCAn acute nursing nurse.
Glazing land
Mehra/ The frontline [ES-SCLC] The setting was largely informed by 2 tests, and both have integrated immune checkpoint inhibitors with our standard backbone from Platinum [therapy] and etoposide. In the [phase 3 IMpower133 trial (NCT02763579)]Patients received atezolizumab [Tecentriq] platinum [therapy] and etoposide, followed by conservation treatment.1 In the [phase 3 CASPIAN study (NCT03043872)]It was largely the same paradigm, but with Durvalumab [Imfinzi] platinum [therapy] and etoposide, followed by maintenance therapy.2 Both studies showed an improvement in overall survival by adding the immune checkpoint inhibitor to standard chemotherapy.
Before these studies, the patients received 6 chemotherapy cycles and were then in a treatment industry. During this time, they are often very quick. Now there are effective treatment options that can be continued and are well tolerated. It has led to a better quality of life and a longer survival for patients in this environment. Often, however, they will ultimately progress.
Rosner/ Despite this wonderful further development of the immune checkpoint blockade, the vast majority of our patients will unfortunately make progress. If you speak a little about what we do in this second attitude, which factors do you think about? And which treatment options are we currently available for patients?
Mehra/ In the second setting Topotecan [Hycamtin] is the historical agent that was used. Lurbinsizedin in recent times [Zepzelca] was also a treatment option, and this has led to improvements to survival in this environment. However, it is also associated with a large part of the toxicity that we often see with cytotoxic therapy.
The latest clinical studies in ES-SCLC
Rosner/ What has developed in this second line [ES-SCLC] Setting lately?
Mehra/ There are a few interesting [trials]. One is that [phase 3 IMforte trial (NCT05091567)]the lurbsedin incorporates as a potential addition to maintenance therapy with atezolizumab.3 This is a randomized study in which you are after the standard induction treatment with platinum and etoposide and atezolizumab [randomly assigned] to ongoing standard therapy or the addition of lurbinsizedin. We are waiting for the results of this study, but that would affect maintenance therapy. And the other approach … is the inclusion of Tarlatamab earlier in the approach treatment environment.
The [phase 2 DeLLphi-301 study (NCT05060016)] Was the key study with Tarlatamab.4 These patients were extensively pretreated; About a third received at least 3 lines of previous therapy, and 70% to 80% had a previous immune checkpoint inhibitor. This was a patient population that had progressed through the standard options. The key feature for the study was that many of the tumors had a DLL3 expression -over 95% had a DLL3 expression, which is relevant for the mechanism of action for this means. It showed encouraging activities. The response rates were 40%, and in this severely pretreated patient population there was a median overall survival improvement to 15 months.
Rosner/ How do these studies affect your decision -making when you see a patient who has progressed in chemoimmunotherapy?
Mehra/ The performance status is the key. The other important factor is whether you have brain metastases or not. We know that Tarlatamab can have activity in the brain, while this may not apply to all other cytotoxic means we could use.
Tarlatamab protocol
Rosner/ What is the protocol when Tarlatamab starts here and works with our community partners?
Meeting/ To start it, the pharmacy needed a lot. You must all have on board, from the administration to the pharmacy to inpatient and outpatient [clinics]. As soon as we were able to get it up, we were successful. Now we are starting to return to the community. It takes time [the community] Time to set up your websites and model what we did after what we did.
Rosner/ What are some challenges you have seen, from the founding of a patient to trying to go to the outpatient surroundings?
Meeting/ [You need to have] A lot of communication with the patient to ensure that he has a complete understanding. The stationary dosage is hard. You have important aes…. Make sure that you have a good, strong understanding of what it brings with the dosage every 2 weeks. We work hard to ensure that the patients, their families and their supervisors understand the intensity of this regime.
Rosner/ Should other institutions be aware of what logistically speaking, especially on the inpatient side?
WHANMAN/ If you start a new therapy, you would like to follow protocols and standardization. What we learned on the way is not to make a uniform model [because] While this 24-hour to 48-hour monitor[ing] Time is important, we learn that you can tell a lot about how someone will react to his second dose after his first dose. Potentially last longer or observe them for certain AEs instead of checking these boxes. “We should do this compared to this time.” Note how to react to this first dose and then monitor you in the second dose [has been helpful].
Rosner/ With regard to the coordination supply, especially in this inpatient environment, who are the most important actors you want to rely on when you start therapy for these patients?
WHANMAN/ Our pharmacists…. They are a large part of our team that helps us build these plans and protocols. As a provider, I ensure that I am in contact with you and the nurses on our unit, for which this was a big change in the exercise. These are new drugs with very different surveillance rates that you have to do. It was a big hurdle to ensure that everyone feels comfortable and know when we continue and how we continue.
AE management
Rosner/ In your experience, what were some examples of the symptoms that were noticed? How are they captured? How are they evaluated? How do you treat them when you notice when you notice you?
WHANMAN/ One of the greatest things we usually notice in patients is the initial confusion. Parts of the Icans rating are generally “Who are you?” “Where are you?” And “Why are you here?” Questions. We noticed that at first, but another thing that we notice with these therapies are these very subtle problems with skill and fine motor skills. They will often see patients who have difficulty writing their names or to fight their utensils when eating dinner or lunch [go to] the bathroom. Everything that is also recorded in our general treatment.
The standard of care is treatment with dexamethasone. In our institution we follow very well to follow the general classification of CRS, which is made available by Tarlatamab. I have found that dexamethasone is efficient to control. We have many patients where we give you 1 or 2 doses of dexamethasone, and these symptoms come loose, which is incredible to see. It is a scary thing, but it's pretty easy to handle when it is caught early.
We take into account the severity of the icans, but we have already involved neurology. We have a [neuro-oncology] Service at our institution, which can give us recommendations about what you think is appropriate. We sometimes start patients [levetiracetam (Keppra)] If the icans are extreme enough and we are concerned that there may be a risk of seizure. At this point we usually consult our neuro-oncology team to lead us in this management.
Rosner/ What are the signs you are looking for in terms of CRS? How quickly do you notice? What do you use to manage that?
WHANMAN/ In my previous practice, the CRS comes a little later. I saw this 12 to 24-hour mark on average. The first character is usually a fever or an increased heart rate. Depending on the severity, we unfortunately had patients with hypotension and strict or chills-frost-das typical CRS infection. We try to decide on the basis of the entire picture. We don't always jump immediately to use something like Tencilizumab [Actemra]But if a little higher is classified, we sometimes have to give it. We also consider the total number of the patient's white blood cells [and ask]”How do you look?” or “Is there anything else that could cause?” Because some of our patients with some bone marrow came to us from previous treatment and also have a higher risk of infection. We have to differ from it.
Rosner/ Especially if [these patients are] start to get a little [hypertension]included with the intensive care team [is good]…. Fortunately, I don't think we are someone at least for Tarlatamab [intensive care unit]But it is something you want to have about the resources to do this. [When educating patients]What are some resources and discussions you go about?
Meeting/ I give you the manufacturer's brochure…. It is designed nicely. I have a detailed overview of the observation period, which is required for both inpatient and outpatient doses. This starts up to 8 hours in the outpatient setting and then gradually cuts back. When we get 5 in cycle, we are up to 2 below [hours]Which is much more beautiful and a little more bearable for patients. It contains CRS information. Emphasize that these first 2 cans [during] The transition from stationary to outpatient is the most difficult [is important]. It gets better and it seems better for people. Concentration on the AES that could happen and ensure that you have a comprehensive understanding of observation and surveillance [is part of our job].
References
- Horn L, Mansfield as, Szczęsna a, et al. First Atezolizumab plus chemotherapy with extensive lung cancer at a comprehensive stage. N Engl j with. 2018; 379 (23): 2220-2229. DOI: 10.1056/Nejmo1809064
- Goldman JW, Dvorskin M., Chen Y. et al. Caspian investigators. Durvalumab, with or without tremelimumab as well as platinum etoposide against platinum etoposide solely in the first line treatment of small cell lung cancer in the extensive stage (caspian): Updated results of a randomized, open, open label study, phase 3-studie. Lancet oncol. 2021; 22 (1): 51-65. Two: 10.1016/S1470-2045 (20) 30539-8
- Manzo A, Sforza V, Carillio G, et al. Lubbinsedin in small cell lung cancer. Front oncol. 2022; 12: 932105. Two: 10.3389/Fonc.2022.932105
- Ahn MJ, Cho BC, Felip e, et al. Dellphi-301 Investigators. Tarlatamab for patients with previously treated lung cancer with a small cell. N tight j. 2023; 389 (22): 2063-2075. Two: 10.1056/nejmoa2307980