Nicholas Wrigley

Promacta improved platelet count in patients with low-risk myelodysplastic syndrome, according to recent research. 

Promacta (eltrombopag) improved platelet counts in patients with low-risk myelodysplastic syndrome (MDS) and severe thrombocytopenia (a condition of low platelets), according to long-term findings from the phase 2 EQOL-MDS trial.

After a median follow-up of 25 weeks, 42.3% of patients treated with Promacta (112 patients) experienced a platelet response, meaning that they experienced an increase in the amounts of platelets, compared with 11.1% of those treated with placebo (57 patients). Of note, MDS can affect the production of platelets, which are blood components that help to form clots and stop bleeding.

Promacta yielded complete responses in 31 patients compared with none in the placebo arm. As of the data cutoff on March 3, 2022, 34% of responding patients in the Promacta arm remain in response; the corresponding figure in the placebo arm was 16.6%.

In total, 25.5% of responding patients lost their platelet response on Promacta. At the 60-month mark, 63.6% of patients were still alive and did not experience a relapse with thrombocytopenia. Clinically significant bleeding was less common with Promacta compared with placebo.

Platelet transfusion independence — meaning that patients did not need to rely on blood transfusions to support their platelet supply — was achieved in 54.3% of patients receiving Promacta, and 35.3% receiving placebo. The median duration of transfusion independence was 32 weeks and nine weeks, respectively.

MDS progression occurred in 8% vs 9% of patients in the Promacta and placebo arms, respectively, though the difference between the two groups was not found to be significant. Evolution to acute myeloid leukemia occurred in 9% vs 7% of patients, respectively, after a median time from treatment start of 13 weeks (range, 11-24) vs 34 weeks (range, 7-133).

“The occurrence of severe thrombocytopenia in patients with low-risk MDS still represents a challenging condition because of the important burden of related (side effects) and the lack of effective treatments. In most countries, only (platelet transfusions) are currently offered to prevent or treat bleeding in these patients. Despite this unmet clinical need, few investigational products have been tested,” the investigators wrote. “(Promacta) has an acceptable toxicity profile and is effective in raising and maintaining [platelet] count and reducing bleeding without any associated risk of MDS progression.”

Investigators enrolled a study population of 169 patients in the single-blind, randomized, controlled EQOL-MDS trial, 165 of whom were included in the modified intention-to-treat analysis after receiving at least a single dose of the study treatment. The most common MDS-related treatments were erythropoiesis-stimulating agents (16.0%), steroids (16.0%) and deferasirox (5.9%).

Across the total enrolled population, the median age was 72 years, and the median duration of MDS was 14 months. Most patients (61.5%) were male (61.5%) and had low-risk disease according to the revised International Prognostic Scoring System (59.2%). Most patients were platelet (69.2%) and red blood cell (72.8%) transfusion independent at baseline.

Patients received oral Promacta or a matched placebo at an initial dose of 50 mg once daily. The dosage was titrated in 50-mg increments every two weeks up to 300 mg to produce a complete platelet response, which was defined as a platelet count of at least 100 × 103/mm3 without bleeding.

The main goals of the study were the duration of platelet response and long-term safety. The difference in time to response, the frequency of platelet infusions during and after treatment, and the duration of transfusion independence were among the secondary end points.

Grade 3/4 (moderate to severe) side effects not related to the blood affected 50 patients treated with Promacta and 11 receiving placebo. A significant difference in nonhematologic side effects between the groups favored placebo. Permanent treatment discontinuation was necessary for 18 patients in the Promacta arm after a median time from baseline of 13 weeks due to severe liver toxicity or persistent grade 3/4 side effects. Both arms had similar incidences of grade 1/2 side effects.

“As expected, patients in the (Promacta) arm had a higher rate of nonhematologic side effects,” the investigators wrote. “Most grade 3/4 (side effects) occurred early during treatment, within the first 24 weeks, and were reversible upon drug discontinuation. However, no differences were reported between the two arms for deaths.”

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Promacta tended to boost platelet counts in patients with low-risk MDS, and helped those patients be independent of transfusions, too. 

Promacta Improves Platelet Count, Transfusion Independence in MDS

Patients with advanced renal cell carcinoma (RCC; the most common type of kidney cancer) of intermediate or poor risk tended to have better outcomes on a regimen consisting of Cabometyx (cabozantinib) plus the immunotherapy drugs, Opdivo (nivolumab) and Yervoy (ipilimumab) compared to placebo plus immunotherapy, according to updated findings from the phase 3 COSMIC-313 trial, which was presented at the 2023 

At the 20.2-month follow-up point, patients given the three-drug treatment lived for an average of 16.9 months before their disease worsened (a statistic referred to as “progression-free survival), compared to 11.3 months in the group that received a placebo in lieu of Cabometyx.

A survival benefit was also observed in the intent-to-treat population, with median progression-free survival values of 15.3 months and 11.3 months in the experimental and placebo groups, respectively, after 17.7 months of median follow-up.

Among patients with intermediate-risk disease in the intent-to-treat population (which mirrors the real-word setting regarding issues like medication adherence), median progression-free survival was 17.9 months in the Cabometyx group, compared to 11.3 months in the placebo group.

For those with poor-risk disease the median progression-free survival was 9.5 months in the Cabometyx arm and 11.2 months in the placebo arm.

The objective response rate (percentage of people whose cancer shrinks or disappears from treatment) was 45% in the intermediate-risk subgroup among those treated with Cabometyx, compared with 36% among those treated with placebo. The disease control rate (DCR), meanwhile, was 88% and 74% in the experimental and placebo groups, respectively. The objective response rate for the poor-risk group was 36% in the experimental group and 38% in the placebo group, and the DCR was 79% and 68%, respectively.

COSMIC-313 enrolled 855 patients with intermediate- or poor-risk renal cell carcinoma according to International Metastatic RCC Database Consortium (IMDC) criteria. They were randomly assigned one of two groups: half of participants received Cabometyx at 40 mg by mouth daily or a matched placebo. Both treatment groups also received intravenous Opdivo and intravenous Yervoy every three weeks for 4 cycles, followed by Opdivo every four weeks for up to two years and Cabometyx by mouth daily.

Roughly 75% of patients were classified as having intermediate-risk disease, with the remaining 25% having poor-risk disease. Most patients in all subgroups had a tumor PD-L1 status — which is the protein that the immunotherapy drugs target — less than 1%.

Nearly all patients experienced some kind of treatment-related side effect. The incidence of moderate to severe side effects was 74% across patients with intermediate-risk disease in the experimental group, compared with 42% across those in the placebo group. The corresponding values were 67% and 38%, respectively, across the poor-risk subgroup.

Treatment-related death occurred in 1% of patients in each group for the intermediate-risk subgroup and 1% vs 2% in the poor-risk subgroup for those in the combination and placebo groups, respectively.

Total treatment discontinuation due to side effects occurred in 14% of those treated with Cabometyx, compared with 5% of those treated with placebo in the intermediate-risk subgroup; it occurred in 5% vs 4% in the poor-risk subgroup.

Regarding overall survival data, follow-up is still ongoing.

The addition of Cabometyx to Opdivo and Yervoy improved outcomes for patients with advanced kidney cancer, according to recent research. 

Nicholas Wrigley

Promacta Improves Platelet Count, Transfusion Independence in MDS

Adding Cabometyx to Immunotherapy Improves Kidney Cancer Outcomes

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