Selective Immunomodulating Microtubule Binding Agents (SIMBA): A Novel Approach To Chemotherapy-Induced Neutropenia - Episode 10
Implications for using plinabulin as prophylaxis against chemotherapy-induced neutropenia alone or in combination with other therapies based on data revealed by the Protective-1 and Protective-2 trials.
Andrew D. Seidman, MD: I was setting you up to talk about that trial, Protective-2. TAC [docetaxel, doxorubicin hydrochloride, cyclophosphamide] isn’t a regimen that I use a whole lot. I tend to be more of a fan of sequential anthracycline taxane administration, but it certainly was a regimen that could put plinabulin to the test. Does it add to pegfilgrastim? Do you want to talk about that trial, Joyce? It’s twice the size of Protective-1: 110 patients per arm, 221 patients in that trial.
Joyce O’Shaughnessy, MD: This is a prospective phase 3 trial for FDA approval. The data have been submitted to FDA. Hopefully, there will be a favorable action on that, led by our colleague Doug Blayney in breast cancer. All the patients got pegfilgrastim based on the standard of care. That’s a must-have with TAC [docetaxel, doxorubicin hydrochloride, cyclophosphamide]. Then it was with or without the plinabulin against IV [intravenous] once every 3 weeks. It was superior. And it was superior in terms of multiple parameters. Duration of severe neutropenia was the primary end point as I recall, Andy, and it was superior.
Andrew D. Seidman, MD: Cycle 1 severe neutropenia 21.6% with plinabulin, 46.4% with pegfilgrastim. The ability to avoid that neutrophil vulnerability gap more than doubled, and that was a statistically significant result. The duration, of course, was also shorter. That was highly statistically significant. The attack isn’t a regimen that I use a lot, but it was certainly a good regimen to demonstrate what plinabulin can do.
Joyce O’Shaughnessy, MD: The only reason we don’t use it, Andy, is because of typhlitis. Why is it typhlitis? Because the neutrophils dropped like a rocket and the pegfilgrastim doesn’t protect the patient. TAC [docetaxel, doxorubicin hydrochloride, cyclophosphamide] is a very effective regimen. If it can be used more safely, we’d use it more. I like it for certain patients. In ER [estrogen receptor]–positive breast cancer, it’s quite good. But we didn’t use it because people could die of TAC [docetaxel, doxorubicin hydrochloride, cyclophosphamide], you know what I mean? This is absolutely mind-blowing to me, I must say.
Andrew D. Seidman, MD: There’s also a non-statistically significant, but intriguing, difference in febrile neutropenia. With TAC [docetaxel, doxorubicin hydrochloride, cyclophosphamide] supported by just pegfilgrastim, 13.7% of patients had a febrile neutropenia vs 4.2% with plinabulin. That’s not statistically significant given the numbers, but that’s tripling of the percentage points with pegfilgrastim as compared with plinabulin. There were also fewer hospitalizations.
Joyce O’Shaughnessy, MD: Home run. This is like 1 of those, “I can’t believe this.” The idea of an IV therapy for 30 minutes—basically there’s no toxicity.
Transcript edited for clarity.