Selective Immunomodulating Microtubule Binding Agents (SIMBA): A Novel Approach To Chemotherapy-Induced Neutropenia - Episode 5

Treatment Options for CIN

Current mitigation and management strategies for chemotherapy-induced neutropenia.

Joyce O’Shaughnessy, MD: For a long time, there wasn’t really any development in this field, but now we do have interesting agents. I just mentioned trilaciclib was recently approved by the FDA for small cell lung cancer for myeloprotection. It is a CDK4/6 inhibitor, which puts the hematopoietic progenitor cells into more of a G0 state right at the time of getting the chemotherapy. It’s given the same day with the chemotherapy, and it kind of [supports] the myeloprotection. Then it wears off, the chemotherapy’s been metabolized and catabolized, and it’s gone. And now the bone marrow can wake back up again. It actually really worked in most….

Andrew D. Seidman, MD: I know in the platinum, etoposide setting in lung cancer, [there was] less cycle 1 severe neutropenia. There were some signals that it was doing other things in the marrow, in terms of having salutary effects on anemia and the need for red blood cell transfusion. That’s the first new class of agents in the supportive care regimen, if you want to call it that. Or maybe this is a class that facilitates care. There is a signal.

Joyce O’Shaughnessy, MD: It’s IV [intravenous] at the time of chemotherapy, and we looked at that as you well know in metastatic triple-negative breast cancer, in a randomized phase 2 study with gemcitabine and carboplatin, with or without the IV trilaciclib. It was either gemcarbo [gemcitabine and carboplatin] alone, or gemcarbo day 1, day 8 scheduled with IV trilaciclib given day 1 and day 8, just along with the chemotherapy vs getting it 2 days for each of the gemcarbo doses, the day before each gemcarbo, and the day of. The primary end point was myeloprotection, fewer days of grade 4 neutropenia, duration of neutropenia, as well as all the other hematologic parameters you just mentioned, Andy. There certainly was a signal there, and there was some decreased severe anemia, some decreased use of blood transfusions. But the study didn’t actually statistically meet its primary end point in that particular context. Though it did with the etoposide and platinum, as you said, in small cell, leading to the approval of it. Interestingly however, the trilaciclib in this randomized phase 2 trial, whether it was given 1 day or 2 days with each gemcarbo, improved survival compared to gemcarbo alone. And the hypothesis there is that putting the immune cells, the cytotoxic T cells for example, and NK [natural killer] cells, etc, putting them in a bit of a G0 at the time of chemotherapy and protecting them, will allow them to be immunologically active. They have all kinds of biomarker data in that regard. That was a side benefit that’s led now to a phase 3 study to look at that. It’s just great that finally, we’ve got some development in this space.

Andrew D. Seidman, MD: Sometimes trials are designed to change practice based on a standard control regimen. One wonders, maybe for proof of principle, if you just need to pick a regimen that causes a whole lot of myelosuppression. This makes me think back to the NSABP B-38 trial, where dose-dense AC [doxorubicin and cyclophosphamide], paclitaxel was compared to TAC, or docetaxel, doxorubicin, and cyclophosphamide. If you think I’m creating a segue, maybe I am, to talk about another novel agent that has created a signal in this space.

Joyce O’Shaughnessy, MD: Big time.

Transcript edited for clarity.