Potential Adverse Effects of Trilaciclib

Ralph Boccia, MD: The most common adverse events that were seen with trilaciclib were fatigue, hypocalcemia, and hypokalemia. If you look at the 2 arms of the study, numerically each was in the 25% range, compared with roughly the 20% range. There’s no huge difference between the placebo arm and the treatment arm. The grade 3s and 4s were on the order of about 5%. Serious adverse events occurred in about 30% of patients. Remember, this is a patient group with extensive small-cell lung cancer, so there’s a lot of pulmonary involvement. We saw a respiratory failure, and we saw a hemorrhage with sharp thrombosis. If you look at the adverse events themselves, we see those same adverse events in the population in general, but 30% of the patients develop them on the clinical trials. Of some 240 patients who were looked at, 9% had to discontinue therapy because of an adverse event. That’s less than 10% of patients who were intolerant of the drug on the clinical trial.

The other thing to look at is the skin effects. It’s 1 of the more common things—about 20% of patients had some cutaneous adverse event. That could be pain, injection site, erythema, or phlebitis. So it’s a drug that can cause some injection site reactions, which is something to be looked out for. Sometimes there could be pain during the infusion itself, and you may have to dilute it more, you may have to stop and flush things through. For about 20% of patients’ injection sites, there is pain on infusions or afterward some phlebitis that can occur because of the irritant nature potentially.

Jim Schwartz, RPh: We’ve learned about the adverse effects that we need to watch for. An important 1 is the incidence of injection site reactions. There’s a 21% incidence of these reactions: phlebitis and thrombophlebitis. If it occurs, it usually has an average of 1 day, but it does make this drug an irritant. As I said, it’s important to dilute this drug and to run it in slowly at first. To pay very close attention, especially if it’s being run through a peripheral line, to make sure that there’s not inflammation or redness. What needs to be done is to stop the infusion and run normal saline through the arm to get the drug out of the vein. Start again if it does resolve. If it’s a peripheral IV [intravenous] being given, rotate the arms each time so you don’t wear out the vein in either arm. And watch very carefully, especially with peripheral IVs, to make sure that that doesn’t develop and to stop it right away.

Ralph Boccia, MD: In the clinical trial, there was 1 patient who developed interstitial lung disease. There’s always this theoretical question that’s asked. However, there aren’t any scientific data to support that when you have 1 patient that developed interstitial lung disease. If you look at the atezolizumab data alone, if you look at the nivolumab data, if you look at the durvalumab data, we see that pneumonitis can occur. You would have to do a biopsy to find out if it was chemical pneumonitis or autoimmune pneumonitis. But the mere fact that only 1 patient of 240 developed interstitial lung disease, of 1 form or another, speaks volumes to the potential pulmonary safety of the drug.

Transcript Edited for Clarity