Reducing Chemotherapy Toxicity Using Trilaciclib in SCLC

Chemotherapy-induced myelosuppression is a challenge when treating extensive-stage small cell lung cancer (ES-SCLC) with chemotherapy. Misty D. Shields, MD, PhD, an assistant professor of clinical medicine and translational medical oncologist at Indiana University School of Medicine, detailed how trilaciclib (Cosela) administered prior to chemotherapy significantly reduces rates of severe neutropenia and other hematological toxicities at a live Case-Based Roundtable event in Texas. The data also showed that its use leads to fewer chemotherapy dose reductions and delays, improving patients' treatment experience and outcomes.

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This article is part 2 of a 2-part series from a Case-Based Roundtable event.

Targeted Oncology: What studies examined trilaciclib for patients with SCLC?

Misty D. Shields, MD, PhD: There were several of the phase 2 studies looking at trilaciclib in extensive-stage SCLC. This is FDA approved, and was FDA approved in 2020 right in the middle of the pandemic. From the prescribing information, it's given 240 mg/m² intravenously [IV]. Remember when you're ordering it that you order for each day. You get 3 days; you do split dosing of etoposide, day 1, 2 and 3. So you want to give that medication every day that you're going to have exposure. So it's 30 minutes prior to each day 1, 2, and 3. It also was studied, which I want to point out, with topotecan. It received the FDA approval for its use based on the data with topotecan given at a high dose, 1.5 mg/m² on days 1 through 5 for IV topotecan. It's a similar fashion to get it as a premedication before that medication.¹

There were interesting baseline characteristics for the original studies looking at smoking history and ECOG performance status. It was more reflective of what we see in the real world, with an ECOG performance status of 2 with SCLC being represented here, and not restricting to just 0 or 1, which we see in a lot of our studies.

Can you discuss the efficacy of the pooled analysis of trilaciclib?

What we saw on the original studies was presented by Jared Weiss, MD, a few years ago when it was published. [Duration of severe] neutropenia was the primary end point, so severe grade 4 neutropenia, and then secondary end points of febrile neutropenia, and then G-CSF administration. Severe neutropenia [with placebo prior to chemotherapy] was 53% vs 11% with trilaciclib, so significantly reducing the incidence of severe neutropenia as well as febrile neutropenia with the use of trilaciclib compared with supportive care. There was less administration of granulocyte colony-stimulating factor [G-CSF], less anemia, less [use of] transfusions, less [use of] erythropoiesis-stimulating agents, less thrombocytopenia, and slightly less [use of] platelet transfusions. I think this is the most significant information in terms of showing it works. What we saw was that it's meaningful for patients by freezing those bone marrow cells, we don't see the damage that we typically see with platinum-based chemotherapy.

What's also interesting is what we see in our clinics [in terms of] dose reductions and dose delays. When we see a patient with those toxicities, we drop the dose. The dose reductions now with the role of trilaciclib, instead of 25% [reducing the dose of] carboplatin, dose was reduced for 2%.² It was 26% vs 6% [reduction, respectively,] for etoposide. In the other studies, it was 35% vs 8% and 31% vs 19%. There were fewer dose delays as well. So you're getting more chemotherapy, you're getting more time on treatment, and you're having fewer adverse events.

How did patients do over the 4 cycles treatment was given?

They looked at the time of these occurrences of G-CSF administration in cycle 1, 2, 3, and 4. The placebo group had a lot of prophylactic and other G-CSF in cycle 2, but not with trilaciclib, so you're not playing catch-up in cycle 2. Whenever you use this, you're actually staying ahead of it. You're able to stay ahead of it for patients in the trilaciclib arm across the board, and all the way through cycle 4. I's cumulative; it's beneficial throughout all 4 cycles of the chemoimmunotherapy.

The data are similar with severe neutropenia and the incidence over time. Cycle 1 was 17% vs 80% with trilaciclib vs placebo with G-CSF administration. Without G-CSF, it was 6% vs 41%, so we're still seeing that benefit. In cycle 4, it was 0% vs 7.5%. This is also meaningful for our patients because of fewer hospitalizations. We're seeing all-cause hospitalizations reduced in trilaciclib, but also chemotherapy-induced myelosuppression or sepsis really being driven down.^1,2

What patients wouldn’t be the right fit for this treatment?

I use [trilaciclib] in every patient. The only patients that I will not use it in is if a patient gets day 2 and day 3 twice-a-day etoposide, because they want to get it at home for those 2 days for whatever reason. It's usually transportation. I'll typically give it on day 1, when they get the carboplatin and etoposide, and then day 2 and day 3, they're getting treatment orally twice a day [at home].

Is trilaciclib cost effective for patients and hospitals?

There is a published study looking at the cost of care.³ We submitted our own data, and it was accepted at the American Society of Clinical Oncology Annual Meeting in 2025. We [did] the cost-effectiveness analysis as well, which is meaningful for pharmacists and infusion centers. I had to meet with my infusion center 3 years ago when I started using this and I said, “Here are the data, let me have a few months to try this.” Now we have it incorporated in all of our order sets and everything. It is cost-effective, both the initial use, but also the complications down the line.

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_{DISCLOSURES: Shields has previously reported membership on advisory committees, review panels, board membership, etc, with AstraZeneca (relationship has ended) and Jazz Pharmaceuticals (relationship has ended), and speakers’ bureau with Jazz Pharmaceuticals (relationship has ended).}

_References:

_{1. Weiss J, Goldschmidt J, Andric Z, et al. Effects of trilaciclib on chemotherapy-induced myelosuppression and patient-reported outcomes in patients with extensive-stage small cell lung cancer: Pooled results from three phase II randomized, double-blind, placebo-controlled studies. Clin Lung Cancer. 2021;22(5):449-460. doi:10.1016/j.cllc.2021.03.010}

_{2. Ferrarotto R, Anderson I, Medgyasszay B, et al. Trilaciclib prior to chemotherapy reduces the usage of supportive care interventions for chemotherapy-induced myelosuppression in patients with small cell lung cancer: Pooled analysis of three randomized phase 2 trials. Cancer Med. 2021;10(17):5748-5756. doi:10.1002/cam4.4089}

_{3. He W, Karkash A, Kumar P, et al. Outcomes with trilaciclib versus granulocyte colony stimulating factor regarding chemotherapy-associated adverse events, dose reductions, and subsequent therapies in small cell lung cancer. J Clin Oncol. 2025;43(suppl 16):e20116-e20116. doi:10.1200/JCO.2025.43.16_suppl.e20116}