Managing T-DXd Adverse Events in the Real World

Managing T-DXd Adverse Events in the Real World

With latest expansions in its breast most cancers indications, there was a rise in the usage of trastuzumab deruxtecan (T-DXd; Enhertu).

“Lots of us are utilizing this extra continuously now than we have been up to now,” defined Sid Yadav, MD, a breast and gynecologic most cancers specialist on the Mayo Clinic in Rochester, Minnesota. Nevertheless, he added that managing its adversarial occasions has been a “little bit of a studying curve for all of us.”

The antibody-drug conjugate has been in the marketplace since 2019 for metastatic human epidermal progress issue receptor (HER2)–constructive breast most cancers, however it was then authorised in Might 2022 for earlier use on this affected person inhabitants and in August 2022 for sufferers with HER2-low illness, This newest approval was based mostly on knowledge displaying an enchancment in general survival that was described as “practice-changing.”

As well as, T-DXd can be authorised to be used in metastatic HER2-mutated non–small cell lung most cancers and metastatic HER2-positive gastric and gastroesophageal junction adenocarcinoma.

Increasing use of this drug has led to rising consciousness amongst oncologists of T-DXd’s appreciable toxicities, Yadav instructed Medscape Medical Information.

Among the many eight or so sufferers he is seen or handled over 2 months, Yadav has already seen one case of high-grade interstitial lung illness/pneumonitis, a complication that “everyone worries about” as a result of the label for T-DXd carries a black field warning of this chance.

There’s been different points at Mayo, as effectively. In a single latest week, 5 sufferers have been admitted for potential T-DXd adversarial occasions, together with neutropenic fever and sepsis; pneumonitis; extreme nausea/vomiting with electrolyte imbalance; pneumonia, and non–ST elevation myocardial infarction with low ejection fraction.

It is unknown what quantity of T-DXd recipients the 5 admissions represented. Yadav’s service has over 10 breast oncologists, so the circumstances may signify perhaps 1%-10% of sufferers, he mentioned.

His expertise prompted Yadav to show to Twitter to ask fellow oncologists what problems they’ve seen with T-DXd.

One mentioned that his “real-world toxicity expertise [has been] worse than the trial knowledge,” which is not uncommon, one other oncologist famous, as a result of real-world sufferers are sometimes sicker than trial members and extra weak to toxicities.

A 3rd oncologist countered that she has “discovered [T-DXd] typically simple for sufferers to tolerate and [has] not wanted to confess anybody” to this point.

General, Yadav mentioned that in his expertise, there are points that should be thought of with T-DXd past interstitial lung illness.

As with all chemotherapy, neutropenia and infections are a priority, because the labeling notes. The interstitial lung illness case has additionally made Yadav have a low threshold to order CT in sufferers with any hints of shortness of breath and to start out steroids if there’s any suspicion.

In all probability the most typical difficulty, nonetheless, is nausea and vomiting. In scientific trials, over 70% of members reported nausea and over 40% skilled vomiting.

In response, Yadav and his colleagues have develop into extra aggressive with prophylaxis. Pre-treatment consists of steroids, palonosetron, and fosaprepitant. Sufferers are additionally normally despatched house with prochlorperazine, ondansetron, and lorazepam. If these do not assist, the workforce considers olanzapine.

They’ve additionally discovered that “it is vital to spend that additional 15-20 minutes upfront” with sufferers earlier than beginning T-DXd to clarify the danger for nausea and vomiting and the way will probably be managed, Yadav commented. “We do chemotherapy educating for each affected person, however I believe we spend extra time [now] speaking about nausea and vomiting with this subset,” he mentioned.

Yadav nonetheless begins sufferers on the usual breast most cancers dose of T-DXd — 5.four mg/kg each three weeks — however mentioned he is faster now to decrease the dose if sufferers aren’t doing effectively. He estimates he is accomplished that a few instances to this point.

Approaches on the Mayo Clinic are according to these in a latest article on managing T-DXd toxicities by Hope Rugo, MD, from the College of California, San Francisco, and colleagues.

These authors conclude that adversarial occasions associated to T-DXd are frequent however are mostly low-grade and manageable. Nausea and vomiting are among the many commonest, and so they observe that interstitial lung illness/pneumonitis is a crucial adversarial occasion, for which proactive monitoring, prognosis, and administration are key.

The evaluate describes administration practices of different healthcare suppliers and establishments with expertise in utilizing T-DXd to assist with secure and efficient administration of the drug’s adversarial occasions, significantly because the period of remedy could also be fairly lengthy.

Correct administration of T-DXd–associated adversarial occasions will enable optimum publicity to and profit from the drug and can assist keep away from untimely discontinuation or improper dose reductions, Rugo and colleagues commented.

Yadav experiences no related conflicts of curiosity.

ESMO Open. August 11, 2022. Full textual content

M. Alexander Otto is a doctor assistant with a grasp’s diploma in medical science and a journalism diploma from Newhouse. He’s an award-winning medical journalist who labored for a number of main information retailers earlier than becoming a member of Medscape. Alex can be an MIT Knight Science Journalism fellow. Electronic mail:

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