Selective Immunomodulating Microtubule Binding Agents (SIMBA): A Novel Approach To Chemotherapy-Induced Neutropenia - Episode 11
A discussion regarding patient selection and indications for using plinabulin, a first-in-class selective immunomodulating microtubule-binding agent, as prophylaxis against chemotherapy-induced neutropenia.
Joyce O’Shaughnessy, MD: I can’t imagine this won’t become available to us from the FDA. Assuming it does, where are we going to use this? Are we going to use single agent? Of course, we’ll have to see what the FDA approves and what the label is. It’s been used in non–small cell lung cancer equally effectively. And the Protective-1 trial, as you said, was in prostate cancer, lung cancer, and breast cancer. It’s being used in lots of clinical trials. It doesn’t make any difference which chemotherapy you get. As long as it causes significant neutropenia. It’s going to be the same thing because it protects the progenitors in the stem cells, in the marrow. So it’s potentially going to be available in combination.
Andrew D. Seidman, MD: Yes. It’s going to be interesting to see how it performs in subsequent trials. In regimens that include not only chemotherapy but also checkpoint inhibitors, the trilaciclib study uses etoposide, carboplatin, and atezolizumab because of some of these T-cell activation and dendritic cell effects. I see that as a potential future avenue for diseases where cytotoxic chemotherapy is paired with immunotherapy. That might be a future use case.
Joyce O’Shaughnessy, MD: There’s a trial ongoing that I’m aware of. I’m fascinated by it. It’s ipilimumab and nivolumab plus the plinabulin. They’ve already demonstrated safety at ASCO [American Society of Clinical Oncology Annual Meeting] this year, and now they’re taking it forward into the melanomas of the world. That will be interesting to put to a randomized trial, plus or minus the plinabulin. But when it comes to serious myelosuppression regimens such as AC [doxorubicin hydrochloride, cyclophosphamide], in older, frailer patients—with all the risk factors we mentioned—I’ll be sorely tempted to add the plinabulin to the pegfilgrastim. Or if I have any concern about patients who would be vulnerable to infection, febrile neutropenia, or diarrhea. They’re at risk for diarrhea because we have patients who have a history of other infections, who’ve recently had infections around expanders. For example, patients who have chronic bronchiectasis.
Andrew D. Seidman, MD: I have patients who are chronically colonized with MAC [mycobacterium avium complex], and I worry about those people.
Joyce O’Shaughnessy, MD: Me too. There are a lot of vulnerable people, and for sure I want them to have every measure of protection. If they’re going to get myelosuppressive treatment, they’re going to get both in my practice. For patients for whom I’m a little concerned about the safety of the pegfilgrastim for the reasons we mentioned, but I would like to give them the opportunity to be protected, to be treated on time, I’ll have them come in and get an immediate dose reduction or an immediate dose delay. With the plinabulin single agent, I hope we have that opportunity because I love those head-to-head data for that more modestly myelosuppressive group of patients. Finally, in the palliative setting, where I don’t know how to give the pegfilgrastim anyway, how easy would it be to give the plinabulin with some eribulin or vinorelbine. You can do that each time because you’re not going to overshoot the market—the marrow is going to wake up, and those cells are going to be functional. They’re put to rest for the brief period of time that the plinabulin is there when the chemotherapy is there. But that could greatly simplify the management of our patients if I don’t know where to give them the GCI. I try this. I try that. It’s a trial by error type of thing.
Andrew D. Seidman, MD: TCHP [docetaxel, carboplatin, trastuzumab, pertuzumab] comes to mind also: docetaxel-carboplatin with HER2 [human epidermal growth factor receptor 2] antibodies, in terms of the potential combination of both myelosuppression and GI [gastrointestinal] mucosal toxicity. Do you give a lot of TCHP [docetaxel, carboplatin, trastuzumab, pertuzumab]?
Joyce O’Shaughnessy, MD: I do.
Andrew D. Seidman, MD: There’s another place. There certainly could be patients who benefit from the addition—or even the substitution of—plinabulin for pegfilgrastim, depending upon whether they’ve experienced severe bone pain or they’ve had febrile neutropenia and cycle No. 2 of TCHP [docetaxel, carboplatin, trastuzumab, pertuzumab]. Are you going to reduce the dose before giving adjunctive curative therapy? For me, that’s another low-hanging fruit.
Joyce O’Shaughnessy, MD: I totally agree. The patients with bone pain, for sure. It’s another opportunity for those patients.
Transcript edited for clarity.