CDK4/6 Inhibition Preserves Multiple Cell Lines in SCLC

Martin F. Dietrich, MD, assistant professor of internal medicine at the University of Central Florida College of Medicine and medical oncologist with the US Oncology Network, discusses the use of the CDK4/6 inhibitor trilaciclib (Cosela) to address myelosuppression associated with chemotherapy in small cell lung cancer (SCLC).

In trials of adding trilaciclib to the standard of care, it not only dramatically reduced the rate of severe neutropenia but also protected against thrombocytopenia and anemia. According to Dietrich, affecting other cell lines besides neutrophils is crucial as patients with SCLC often have cardiovascular and pulmonary comorbidities that are worsened by low hemoglobin levels, but don’t always reach the level of anemia that requires red blood cell transfusion or other direct intervention.

Dietrich says that preventing myelosuppression in multiple hematopoietic cell lines bolsters quality of life for these patients all-around, making this an important approach in SCLC.

TRANSCRIPTION:

0:10 | CDK4/6 inhibition is very broad in terms of bone marrow protection. We had three studies, 2 in the first-line setting. And here I want to focus particularly on those that included chemotherapy plus immunotherapy, our current standard of care in the first-line setting with a placebo-controlled arm vs trilaciclib. I think that's a very interesting one, we see about 50% rate for severe neutropenia, meaning a neutrophil count of 500 or below without trilaciclib. Now if we deploy trilaciclib in the intervention arm, this percentage goes down to 2% and we see very similar levels of protection for platelets, and also a very strong improvement in the development of anemia and severe anemia. So we reduce the number of patients with anemia and also the severity of anemia at the same time.

1:04 | Obviously, those are number improvements. This is an important factor, and we want to keep our patients safe. But aside from basically eradicating neutropenia as a major concern and making it a rare occurrence with this protective strategy, we're also affecting other cell lines that are important. I do want to point out anemia is a cell line of particular concern, and we think about our patients with small cell lung cancer, typically older, typically with both cardiovascular and pulmonary comorbidities, COPD, [and] coronary artery disease, so the impact of anemia is exponential in a patient with a reduced cardiopulmonary capacity. We oftentimes have patients with a hemoglobin of 9 or 10 [g/dL]. We rarely ever effectively intervene. We usually don't have opportunities to transfuse. The levels are typically too high. Growth factors don't really work in chemotherapy-induced myelosuppression in small cell lung cancer. So we're really sitting here between an unacceptable level of hemoglobin that affects patients' quality of life and a level that we can't really effectively intervene upon.

2:10 | So prevention here is a major strategy to prevent patients from having to endure the negative impact of anemia and obviously the protective effect of thrombocytopenia and bleeding events, [and] reduce transfusions. I think this is important on the numbers game, but it also affects I think this is the most important part, it's not only just correcting numbers, but it really affects patients' quality of life. And we see a preserved functionality, preserved anemia, fatigue index. We have a number of patient-centric measures that we are improving in a treatment. I think that's equally important. We want to make sure that the patient is safe. Obviously, neutropenia has been managed successfully with G-CSF, but we're really getting a much more comprehensive 360 [degree] view on myelosuppression in small cell lung cancer and trilaciclib here can make a significant impact.