Small-Cell Lung Cancer - Episode 3
Stephen V. Liu, MD, and Jared Weiss, MD, share their thoughts on the impact of the recent approval of trilaciclib prior to platinum/etoposide-based chemotherapy for the treatment of ES-SCLC.
Stephen V. Liu, MD: Trilaciclib is an intravenous [IV] CDK4/6 inhibitor. It is approved as a myeloprotective agent given with chemotherapy for small cell lung cancer. We know that the primary toxicity with platinum/etoposide is myelosuppression, and trilaciclib was shown to reduce myelosuppression, decreasing neutropenia, reducing the need for transfusions. We don’t know if this will impact the rate of febrile neutropenia or the rate of hospitalizations, which I would say have more clinical impact. But I would say that it is a reasonable addition to therapy for patients who are particularly at risk. For me it does not influence first-line treatment, as the benefit I think would extend across the different available first-line regimens. While it is a reasonable addition, it is not part of my practice.
Jared Weiss, MD: Trilaciclib is a short-acting IV CDK4/6 inhibitor. The idea is to keep the bone marrow progenitors out of cycle while the chemotherapy is washing by. This was first studied in extensive-stage small cell lung cancer because small cell is Rb null. That means that the cancer, for better and for worse, will not be affected by the agent. And any effects that you see are going to be related to the myeloprotection benefit.
Before diving into study design and results, I would like to disclose that I’ve been involved in these research efforts, and I’m unabashedly enthusiastic about the agent. That enthusiasm comes out of the quality-of-life data that I’m going to describe for you. Trilaciclib was studied in 3 randomized phase 2 efforts: carboplatin and etoposide with or without the drug; [carboplatin, etoposide, atezolizumab] with or without drug; and topotecan with or without drug.
Then looking at each of the individual studies or the combined analysis, which should be in the press within days, what you see is a myeloprotection benefit. All of the blood counts are protected. And the story is clean; it’s not just a numeric effect. The myeloprotection in terms of the numeric improvement in counts translates to a reduction in adverse events, of course driven mostly by the events you would expect for myeloprotection, but also interestingly alopecia as well. That reduction in adverse events translates to a reduction in supportive-care use, like blood transfusions and Neulasta use. And critically, all of this translates into an improvement in quality of life as determined by patient-reported outcomes. The one that impressed me the most is fatigue. By patient report, fatigue was decreased with the addition of trilaciclib to standardized chemotherapy. This is important to me because in my practice, fatigue is the effect that my patients suffer from the most, and it’s the one that I’m most unable to help with. We have very few agents that help with fatigue. In my practice, now that the agent is approved and once it becomes available, will be that every patient with extensive-stage disease who gets carboplatin/etoposide and atezolizumab, or who gets topotecan, will have it preceded by trilaciclib.
Transcript Edited for Clarity