Just because there is an FDA approved treatment, should it be offered to everyone?

Dr Tolaney from the Dana Farber Cancer Institute presented data (GS1-05) exploring whether it’s appropriate to use the monoclonal antibody T-DM1 to treat early stage HER2+ breast cancer. Even though patients with HER2+ breast cancers that are 3cm or smaller and haven’t spread to the lymph nodes have a very good prognosis, with 93% disease free survival at 7 years, there is concern that some 10-30% of early stage HER2+ breast cancers recur.

The ATEMPT trial enrolled 512 patients with early stage HER2+ breast cancer. The majority had high-grade tumors and 75% hormone positive disease. Participants were randomized 3-1 to receive either T-DM1 for one year (383 patients) or the standard of care, which is Herceptin plus the chemotherapy paclitaxel (114 patients). The study design looked at two endpoints: how this patient group fared when treated with T-DM1 compared to standard of care, and whether T-DM1 had fewer side effects. Note: because of the 3-to-1 study design, it was not powered to find the efficacy for the control arm. The primary interest for the researchers was to find a less toxic alternative to Herceptin and chemotherapy for this patient group.

Median follow up was 3 years, and 97.7% of patients treated with T-DM1 were alive without a breast cancer recurrence (disease free survival). Two patients experienced spread (distant recurrence) and three died from non-breast cancer specific causes.

Given the current standard of care for early-stage HER2+ breast cancer also does a good job of preventing recurrence, researchers really wanted to know if fewer side effects for T-DM1 would make it a superior choice. The data showed that around half (46%) of all patients experienced toxicity from their treatments, regardless of which treatment they were given. However, more patients given T-DM1 discontinued treatment because of severe toxicity: 17% of patients given T-DM1 versus 6% given Herceptin plus chemo.

The specific toxicities of the different treatment arms were different. Fatigue was similar for both groups, with around a quarter of patients reporting fatigue. Patients receiving Herceptin and chemo experienced more neuropathy and neutropenia, and they were more likely to lose their hair. People on T-DM1 were more likely to have low blood platelet counts and problems with liver function. These serious toxicities caused two and a half times as many people to stop taking T-DM1 before completing treatment. 

Given T-DM1 (brand name Kadcyla) comes with serious toxicity and costs around $10,000/month, you can imagine my shock when the presenting researcher concluded that despite the fact that T-DM1 does not have fewer toxicities than Herceptin and chemo, some patients may prefer to be given T-DM1, especially if they are concerned about hair loss! This narrow view of toxicity ignored the significant financial toxicity of expensive treatments. The reality is, when doctors are discussing treatment choices, they virtually never include differences in price in their conversations with patients.

We need safe, effective, and affordable breast cancer treatments, and T-DM1 for early stage HER2+ breast cancer is not that.