Jorge Nieva, MD, is an associate professor of Clinical Medicine at the Keck School of Medicine of the University of Southern California

Jorge Nieva, MD, discusses the current role and the effect antibody-drug conjugates have on the lung cancer treatment paradigm.

Dr Nieva on the Role of ADCs in the NSCLC Treatment Paradigm

“It’s natural to try to find the best drugs to partner with TKIs in order to try to maximize those [improved] outcomes. Antibody-drug conjugates represent a new way of delivering chemotherapy with more pharmacokinetics [and] continuous exposure of the tumor cells to the drug, and there may be many advantages to doing that over free chemotherapy administration.”

Jorge Nieva, MD, an associate professor of clinical medicine at the Keck School of Medicine of the University of Southern California, discussed the effect antibody-drug conjugates (ADCs) have on the non–small cell lung cancer (NSCLC) treatment paradigm.

There are potentially more studies that will evaluate frontline ADCs for the treatment of patients with lung cancer who have actionable genomic alterations, Nieva began. He noted that data from the phase 3 FLAURA2 (NCT04035486) and MARIPOSA (NCT04487080) trials have demonstrated that an intensified regimen could lead to improved outcomes, particularly in patients with 

-mutated NSCLC. Determining the best drugs to pair with TKIs to maximize improved outcomes is natural, he added, especially as ADCs represent a new way of delivering chemotherapy with more pharmacokinetics than traditional delivery modalities and continuous exposure of the tumor cells to the drug, he emphasized. Furthermore, with TKIs alone, patients could eventually develop resistance, although cytoreductive strategies could help prolong time to resistance, whether it’s with chemotherapy, radiation therapy, or surgery, he contextualized. Additionally, for patients who choose to be more aggressive with their cancer treatment, it’s important to add cytoreductive agents, Nieva noted.

International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer

 revealed that osimertinib (Tagrisso) plus pemetrexed and carboplatin or cisplatin led to a statistically significant and clinically meaningful overall survival improvement compared with osimertinib monotherapy for the treatment of patients with 

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Dr Nieva on the Rationale for Comparing ALK Inhibitors in ALK+ NSCLC

“Many of the [oncologists] in the room thought the best approach was to use lorlatinib because it’s the most powerful drug, but use it as a reduced dose. Others felt that it needs to be an individualized decision that the patient makes after a discussion of risks and benefits.”

Jorge Nieva, MD, an associate professor of clinical medicine at the Keck School of Medicine of the University of Southern California, discussed key clinical implications from matched-adjusted indirect comparison (MAIC) data evaluating the efficacy and safety of crizotinib (Xalkori) vs alectinib (Alecensa), brigatinib (Alunbrig), and lorlatinib (Lorbrena) in patients with 

-positive non–small cell lung cancer (NSCLC).

-positive NSCLC is a relatively rare molecular subtype, and consequently, there is a limited number of large-scale randomized clinical trials directly comparing the full range of approved ALK inhibitors, Nieva began. Most available data stem from studies in which individual agents have been evaluated against crizotinib, a first-generation ALK inhibitor, serving as a common comparator across multiple trials, he explained. This has enabled the application of MAICs as a method for formally assessing the comparative efficacy of newer agents, despite the absence of direct head-to-head trials, he noted. MAIC methodology involves statistical adjustment of patient-level data to account for differences in baseline characteristics—like age, sex distribution, race, and key prognostic indicators—between trial populations, he said. When performed appropriately, this method allows for more reliable cross-trial comparisons by harmonizing patient demographics, enabling a more accurate assessment of treatment effect size relative to a common comparator, he emphasized.

Although all next-generation ALK inhibitors have shown efficacy benefits over crizotinib, in MAICs between these ALK inhibitors, lorlatinib appears to provide the greatest incremental improvement in PFS compared with alectinib and brigatinib, as reflected by its hazard ratio in indirect comparisons. However, this enhanced efficacy is counterbalanced by a higher incidence of treatment-related adverse effects, particularly neurocognitive toxicities, he cautioned. These may manifest as alterations in mood, personality, memory, or general cognitive function and can significantly impair a patient’s quality of life, he stated.

 meeting, the therapeutic choice between ALK inhibitors should involve a nuanced, individualized approach, Nieva emphasized. Although many oncologists advocate for the use of lorlatinib as first-line therapy due to its potent central nervous system activity and robust efficacy profile, some recommend initiating treatment at a reduced dose to mitigate toxicity, he added. Others emphasize shared decision-making, incorporating a comprehensive discussion of benefits and risks with the patient to determine the most appropriate therapeutic course, Nieva concluded.

Jorge Nieva, MD, discusses matched-adjusted indirect comparison data evaluating crizotinib vs alectinib, brigatinib, and lorlatinib in ALK-positive NSCLC.

Jorge Nieva, MD, associate professor, clinical medicine, Keck School of Medicine, University of Southern California, discusses the rationale and design of an ongoing phase 2 trial (NCT05340309) investigating a telemedicine approach to delivering subcutaneous atezolizumab (Tecentriq) for patients with non–small cell lung cancer (NSCLC), which he presented at the 2023 IASLC World Conference on Lung Cancer.

Cancer care has undergone several changes because of the COVID-19 pandemic, Nieva says. Notably, many patients with cancer became hesitant to visit hospitals for infusion therapies during this period, Nieva emphasizes. In response to this issue, Nieva and colleagues designed a study that would enable patients to receive infusional treatments at home.

Monoclonal antibodies are known to be safe and effective when administered subcutaneously, and they are frequently administered at home. This makes them ideal candidates for home-based administration in this study, Nieva explains. The single-arm study is enrolling patients with NSCLC who are eligible to receive atezolizumab for standard indications, Nieva notes. Eligible patients include those with previously untreated, locally advanced or metastatic disease with PD-L1 expression on at least 50% of tumor cells and no 

 aberrations; those with metastatic disease that has progressed during or after treatment with platinum-basedchemotherapy, including those with 

 aberrations who have progressed on FDA-approved therapies; and those with stage II to IIIA disease who have undergone resection and platinum-based chemotherapy, and whose tumors express PD-L1 on at least 1% of cells. Patients’ ability to comply with this study is contingent on their ability to use smartphones.

This trial plans to enroll 37 patients. After technology training, patients will undergo liquid biopsy and in-office administration of subcutaneous atezolizumab, followed by home administration of the agent. Patients with metastatic disease will continue this treatment for up to 2 years. Patients receiving subcutaneous atezolizumab as adjuvant therapy will continue treatment with the agent for up to 1 year.

Jorge Nieva, MD, discusses the rationale and design of an ongoing phase 2 trial  investigating a telemedicine approach to delivering subcutaneous atezolizumab for patients with non–small cell lung cancer.

Dr Nieva on the Rationale for Investigating At-Home Atezolizumab Administration in NSCLC

As the role of supportive care and small cell lung cancer treatment, expands, what are your practical takeaways that you have and things you'd like to see emphasized in future and continued analyses of chemotherapy induced myelosuppression?

In the future, we certainly want to see more studies that use different regimens in combination with trilaciclib. Currently, we're really only using it in patients with extensive-stage small cell lung cancer, with a carboplatin etoposide backbone. In the future, we should see more studies, more research done on expanding this to other regimens because myelosuppression is not a problem exclusively in this particular regimen and this particular patient population. We want to see all of our patients have the benefit of as little myelosuppression as possible so long as we know that supportive care intervention doesn't affect outcomes negatively. We have so far a pretty good track record in our first indication with this medication. Hopefully, we'll start to see more expansion.

 Absolutely. Thank you, Dr. Nieva, for this discussion. Before we conclude, I would like to get your closing thoughts on unmet needs and future perspectives on the treatment of patients with small cell lung cancer.

Patients with] small cell lung cancer, unfortunately, a large percentage of them don't get cured with the original regimen. We really need to start looking at second-, third-line regimens that improve outcomes, and making second- and third-line regimens as tolerable for patients as much as possible.

 The major advances we've had more lately have been with the addition of immunotherapy but that also, as you said, doesn't always affect or help a lot of patients as much as we'd like to, so looking at new strategies to sort of enhance the durability of treatment for extensive stage small cell lung cancer patients, and also making it more tolerable are really important and possibly doing some more targeted therapies as we've seen, some indications that we may be able to do at this ASCO [American Society of Clinical Oncology] would be really important. Thank you again, to our viewing audience, we hope you found this OncLive® Insightsdiscussion to be useful and valuable to the treatment of your patients with small cell lung cancer.

Jorge Nieva, MD, and Ashish Saxena, MD, PhD, discuss the possibility of expanding the use of supportive care regimens to reduce the effects of myelosuppression in patients with SCLC.

Takeaways and Considerations for the Future in the Treatment of SCLC

For your practice, how do patients respond to getting these supportive care measures? When do you think is the best way to introduce supportive care for patients? Do you have any examples of how you may have done this with your patients?

I really think it's important to standardize. At our institution, we try to make the supportive care plan standardized to every chemotherapy regimen. You don't want to mismatch and use the wrong antiemetics if you're using highly emetogenic chemotherapy, and by the same token, if you're giving very myelosuppressive chemotherapy, you really should default to using an optimal strategy for supportive care, whether that's growth factors or trilaciclib. One interesting story that I have around that is that I was taking care of a patient, and they were treated with our standard approach, which incorporated trilaciclib for their first cycle, and then they couldn't get it in their second cycle for a variety of different reasons. That really made a profound difference in how the patient was feeling, what happened with their overall counts, delays for the subsequent cycle. As you know, dose intensity is also important. That really brought it home to me that making sure that that were as standard as possible and as regular as possible in how we incorporate these medications is important.

I agree totally, and I've had experiences before trilaciclib. I had given chemotherapy, and the patient comes back for a follow-up, and they're a little anemic and not feeling great. But then they say, “OK, maybe she got a transfusion”, and they're like, "Well, I have to wait now, I have to get my typing screen, I don't want to wait here, so I'm going to go home, I'll be OK." Then the next thing is, they say, "Well, I felt worse, I had to go to the emergency room. And now I'm getting transfused there." Which makes you feel like, "Oh, if I could have prevented all of this, it would have been so much better than having to go through these things."

We've talked a little bit about costs. In addition to reducing chemotherapy induced myelosuppression, improving quality of life supportive care with trilaciclib, it has been shown to be cost beneficial as well. Can you reflect on how factors like quality of life and cost burden can influence your treatment decisions and considerations?

Cost is a big thing we've seen, especially in oncology, the cost of medications and treatments are really high. It can cost the patients in terms of the treatments and what's covered by insurance. Having a treatment option that has been shown in studies to be cost effective by preventing the complications of myelosuppression, whether it's having to come back in and get transfusions or antibiotics if you're neutropenic, going to the hospital with neutropenic fever, so preventing all that has been shown to save money. That's really important for general economic well-being of our medical system. In addition, we talked about quality of life, and whether the patient's feeling better, and they also will feel better if they're not having huge expenses that they may have to pay some of out of pocket.

Jorge Nieva, MD, and Ashish Saxena, MD, PhD, consider the broader impact of supportive care on cost burden and quality of life and share scenarios in which supportive care is most appropriate.

Practical Considerations Regarding the Incorporation of Supportive Care Into Practice

In addition to reducing the incidence of myelosuppression, studies have also shown that it does help improve quality for the patients. Can you discuss how you feel the importance of these things, of fatigue and blocking those things, and how supportive care measures can help with that?

Quality-of-life metrics are a great way of balancing the risk-benefit ratio of any medication. Obviously, all medications bring with them some degree of toxicity and trilaciclib is not an exception, but it has benefits. In order to figure out how to balance those risks and benefits, we often turn to our quality-of-life tools. When the quality-of-life tools show that overall quality of life is better with a particular medication, it gives a lot of confidence to clinicians that what you're doing is something that really is affecting the patients in a favorable way that they can perceive and that they can perceive these benefits from the medications. How do you view the value of patient-reported outcome studies, and how do you weigh these findings in your treatment approach?

I think the patient-reported outcome studies are really important because they give some concrete evidence [that] the patients are actually feeling better. Sometimes for us, it's sort of a nebulous, "Are you feeling better?"When we do proper studies to actually show this, and there are methodologies to do this and provide that data, as you said, it gives the clinician confidence that what you're doing is actually having an impact.You can tell the patients that, "Listen I'm going to give you this, and studies have shown that it does make people feel better, and it does improve their quality of life." It is important. There were talks at ASCO [American Society of Clinical Oncology] this year about how we should be paying a little bit more attention. We gather all this quality data and a lot of studies, but we are not really using that information. I think they're important for practice.

Jorge Nieva, MD, and Ashish Saxena, MD, PhD, share insights about the value of patient-reported outcomes studies and the extent to which they can shape treatment decisions.

Quality of Life and Patient-Reported Outcome Measures in SCLC Treatment

 How have approaches to myelosuppression evolved in recent years, especially in extensive stage, small cell lung cancer?

We were, typically and historically, treating it the way we do in other tumor types with G-CSF [granulocyte colony stimulating factor], sometimes prophylactically, but a lot of times playing catch up, where when people got to anemic or thrombocytopenic, you may have to give them platelet transfusions. There has been use of things like erythropoietin stimulating agents for anemia, and thrombopoietin receptor agonists for thrombocytopenia, but then we're sort of doing something for each line of blood cells. Then again, as I said, doing transfusions, but more recently with drugs, specifically, trilaciclib, which is CDK4 inhibitor, that when given appropriately before each dose of the chemotherapy transiently arrests hematopoietic stem cells and progenitor cells, to protect them from the effects of chemotherapy. That's become now FDA approved to help prevent myelosuppression induced by chemotherapy. That's been the more recent development in this. We are wondering what you think of as the role of supportive care in myelosuppression, particularly in light of things like shortages for blood products, like platelets and red blood cells?

 I think we need to be good stewards of resources, and that includes our blood resources. To the extent that we can make sure that our patients have as little impact from myelosuppression as possible, have as few transfusions as possible. That goes a long way to ensuring that our patients can have the best outcomes.

 A recent study that aimed to characterize the population pharmacokinetics of trilaciclib found that its use resulted in optimal myeloprotective effects with no impact on the antitumor effects of chemotherapy. In light of these findings, and others, demonstrating the utility of cyclin- dependent kinase 4/6 inhibition [CDK4/6], how do you incorporate supportive care into practice? And what are some of the practical considerations of its use?

As you said, we really want to help the patients with supportive care and protection from myelosuppression, because it does translate into them feeling better. I use trilaciclib in our practice. We use it the way it's supposed to be given before chemotherapy, so we have built it into our practice, as we give patients antinausea medicines before they get chemo or fluids in for certain chemotherapy regimens. We use trilaciclib, and giving it the right way, remembering to give it with each dose of the chemotherapy, is important. We’re also educating the patients, since sometimes they don't even realize they're getting it, because for them, it's just part of the cocktail before they get their chemotherapy.

Now, that same study showed that higher exposure did increase the probabilities of adverse events, such as headaches, phlebitis, thrombophlebitis, and injection site reactions. When evaluating the use of supportive care, what are some of the factors you consider when it comes to safety and risk-benefit ratio?

One of the things is that, with your supportive care measures, you don't want to impact the efficacy of the treatment that you're giving, the chemotherapy. Sometimes we worry about certain things, giving them a bit might block the effectiveness of the chemotherapy.There may have been a concern that you're giving a CDK4/6 inhibitor to arrest the blood cells, but maybe it will also protect the cancer cells from the chemotherapy effects. But, as the study you mentioned showed, it didn't seem to do that. That's an important thing. Cost is an important thing. For supportive care, we want it to be costefficient and costbeneficial. Finally, it's supposed to do what we want it to do, which is support the patients. It should help them not have too many side effects from it, but also make them feel better and have good outcomes in terms of supporting their ability to get through the cancer treatments.

Jorge Nieva, MD, and Ashish Saxena, MD, PhD, talk about factors to consider when weighing the risk/benefit ratio associated with the use of cyclin-dependent kinase 4/6 inhibition. 

The Role of Supportive Care in the Management of Myelosuppression in Patients With SCLC

 Hello, and welcome to these OncLive Insights®, titled “Supportive Care Strategies for Chemotherapy-Induced Myelosuppression in Patients With SmallCell Lung Cancer.” I am Jorge Nieva, from the University of Southern California Norris Comprehensive Cancer Center, and I'm joined today by my esteemed colleague, Dr. Ashish Saxena, and I would like to welcome him to introduce himself.

 Hi, thanks,George [Jorge]. I'm Ashish Saxena, I'm a thoracic medical oncologist at Weill Cornell Medical College, Meyer Cancer Center.

Welcome, and thank you for joining me. Today we're going to review the impact of myelosuppression in patients undergoing chemotherapy for smallcell lung cancer, with an emphasis on the use of supportive care for the treatment of myelosuppression. We'll also explore some newer data on supportive care treatments and consider how these data are reshaping the standards of care in the field. Let's get started. Dr Saxena, what are the most significant challenges when it comes to management of patients with smallcell lung cancer?

One of the things we see with patients with particularly extensive stage and metastatic smallcell lung cancer is that they can be quite sick from tumor burden. They have a lot of symptoms from their disease. A lot of times we end up treating them even in the hospital when they come in. That's definitely a challenge. The standard treatment still relies on chemotherapy for both in the first line and in later lines. Immunotherapy has definitely made some improvements in that, but we still use chemotherapy as a backbone. The chemotherapy is with carboplatin and paclitaxel, so you have 3 days paclitaxel, so they're getting 3 days, every day coming in for treatment, so that can be a challenge. With all that chemotherapy comes all of the side effects that we're well aware of with nausea, fatigue, and then chemotherapy-induced myelosuppression. And I'm wondering what your thoughts are about the impact of chemotherapy-induced myelosuppression on the daily lives of the patients?

As oncologists, we often underestimate the impact of fatigue, the impact of mouth sores, and other problems that really go along with myelosuppression. I've had mouth sores before and they're really uncomfortable and having them with chemotherapy is oftentimes very profound. I think the extent that we can use supportive care medications, to make the chemotherapy experience better for our patients, is important. Our patients also experienced a lot of fatigue associated with anemia. People don't feel well, oftentimes, when they're thrombocytopenic. Those of us who have treated for immune thrombocytopenia can often recall how patients, when their platelet counts are low, they just don't feel right. I think trying to mitigate all aspects of myelosuppression should be an important factor when we're treating our patients.

Jorge Nieva, MD, and Ashish Saxena, MD, PhD, discuss the impact of chemotherapy-induced myelosuppression on patients with SCLC. 

Jorge Nieva, MD

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