Will Pizii

Keytruda (pembrolizumab) in the adjuvant setting significantly improved distant metastasis-free survival (time from treatment assignment to first distant metastasis or all-cause death) when compared with a placebo in patients with resected stage 2B or stage 2C melanoma, according to recent study results.

The results — which were presented at the 2022 American Society of Clinical Oncology Annual Meeting — demonstrated that Keytruda had a distant metastasis-free survival rate of 88.1% at 24 months, compared with placebo at 82.2%. The 12-month distant metastasis-free survival also favored Keytruda at 94.7%, compared with 90.2% for placebo.

The study included 976 patients who received either Keytruda (487 patients) or placebo (489 patients) and were stratified by tumor category 3b, 4a and 4b, as well as pediatric status.

Distant metastasis-free survival favored Keytruda across all tumor subcategories. The number of events in the 3b subcategory was 23 in patients receiving Keytruda and 31 in patients receiving placebo, for tumor type 4a it was eight and 20, respectively, and for tumor type 4b it was 30 and 41, respectively. No median distant metastasis-free survival rate was reached; however, the 12-month and 24-month rates favored Keytruda in all of these subgroups.

Fewer distant metastasis events were recorded for the Keytruda group at first recurrence compared with placebo. Forty-five patients (9%) in the Keytruda group and 79 patients (16%) in the placebo group experienced distant metastasis at first recurrence. However, a similar number of patients across both groups experienced distant metastasis events after locoregional occurrence: 18 patients (4%) with Keytruda and 16 patients (3%) with placebo. Most events could be found in the lungs (100 patients) affecting 49% of patients receiving Keytruda vs 73% of patients receiving placebo.

Recurrence-free survival (time from treatment assignment to first recurrence or all-cause death) also favored patients who received Keytruda.

At a median of 37.2 months, patients in the Keytruda group had 95 events (19.5%) vs 139 events (28.4%) events in the placebo group. The 24-month recurrence-free survival rate favored Keytruda (81.2%) vs placebo (72.8%). Similarly, Keytruda had favorable recurrence-free survival rates across all tumor subcategories, and the 24-month recurrence-free survival rates favored Keytruda vs placebo.

Side effects occurred in 83% of patients in the Keytruda group and 64% of patients in the placebo group. Severe or worse side effects occurred in 17% and 5% of patients, respectively. Seventy-seven (16%) patients taking Keytruda discontinued treatment due to side effects.

The side effects reported were typical of this treatment. However, Dr. Georgina V. Long, chair of melanoma medical oncology and transitional research at The University of Sydney, commented during the presentation: “Please note that fatigue in the placebo arm was 19% and 21% in the Keytruda arm, as was pruritis 11% in the placebo arm and 25% in the Keytruda arm.”

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Keytruda, an immunotherapy agent, demonstrated significant improvement in both distant metastasis-free survival and recurrence-free survival compared to placebo. 

Keytruda Demonstrates Significant Improvement for Some Patients with Melanoma 

Patients with hormone receptor (HR)-positive breast cancer who were previously heavily pretreated with CDK4/6 inhibitors achieved encouraging responses after receiving Faslodex (fulvestrant) plus the novel CDK7 inhibitor samuraciclib, according to recent study results.

Moreover, the data, which were presented at the 2021 San Antonio Breast Cancer Symposium, suggested that TP53 mutational status was predictive of outcomes with samuraciclib.

Historically, patients with HR-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer have poor prognoses following disease progression after treatment with CDK4/6 inhibitors.

“On average, we get about a two-month progression-free survival with (Faslodex) in patients who’ve become resistant to CDK4/6 inhibitors,” lead study author Dr. Charles Coombes, director of Cancer Research at Cancer Research UK Imperial Centre in London, said during a presentation of the data.

Additionally, Coombes noted that although patients tolerate hormonal therapy well, efficacy is limited after CDK4/6 inhibitor therapy.

A once-daily, oral, small molecule selective inhibitor of CDK7, samuraciclib has shown synergistic activity with hormonal therapy in HR-positive breast cancer models. In particular, the drug shows activity when combined with the estrogen modulator tamoxifen or Faslodex.

The aim of this study was to identify the appropriate dosing regimen of the samuraciclib plus Faslodex combination and to investigate signs of preliminary activity and biomarkers.

The study comprised 31 patients (median age, 60 years; range, 41 to 81). The study participants received either 240 milligrams (mg) of samuraciclib by mouth once daily plus 500 mg of Faslodex every four weeks (6 patients) or 360 mg of samuraciclib by mouth once daily plus 500 mg of Faslodex every four weeks (25 patients).

Enrolled patients must have been aged at least 18 years, had a confirmed histology of metastatic or locally advanced ER-positive and/or PGR-positive, HER2-negative breast cancer. Patients must also have received prior treatment with CDK4/6 inhibitors, at most one line of chemotherapy or at most two lines of endocrine therapy and have had no prior exposure to Faslodex.

At 24 weeks, the study authors observed a clinical benefit rate (percentage of patients who achieve a complete response, partial response or have stable disease for at least six months) in 36% of patients. The results also showed that patients without liver metastases achieved a clinical benefit rate of 55%. Coombes noted that the clinical benefit rate rose from 36% to 53% when excluding patients with a TP53 mutation.

Of the 25 evaluable patients, 72% achieved tumor shrinkage. Additionally, in 19 patients expressing the TP53 wild type and six patients expressing TP53 mutant type, the median progression-free survival (or the time during and after treatment when the patient lives without disease progression) was 32 weeks and 7.9 weeks, respectively.

After arranging patients based on some of their clinical characteristics, the investigators observed that a median progression-free survival was not yet reached in the 17 patients who had no liver metastases; in the 14 patients with liver metastases, the median progression-free survival was 11.9 weeks.

Liver metastasis is a known risk factor for poor prognosis in HR-positive breast cancer. Future studies are planned to evaluate whether the presence of liver metastases is predictive for samuraciclib-based therapy.

The most common side effects were reversible, low-grade gastrointestinal (GI) events. The most common side effects were diarrhea (90%), nausea (81%), vomiting (74%) and fatigue (36%). The most common serious or severe side effects included diarrhea (19%) and nausea (10%).

The Food and Drug Administration, according to Coombes, has granted this combination fast-track status. Drugs given fast track status are treatments that may address unmet medical needs in serious or life-threatening conditions and may be given expedited reviews.

Future clinical studies are expected to evaluate samuraciclib in combination with oral selective estrogen receptor degraders to extend the limited progression-free survival of a single–agent endocrine therapy.

This article originally appeared on OncLive as 

Samuraciclib Plus Fulvestrant Improves PFS in Heavily Pretreated HR+ Breast Cancer

The use of Faslodex plus the investigational drug samuraciclib was considered safe in individuals with heavily pretreated hormone receptor-positive breast cancer.

Will Pizii

Keytruda Demonstrates Significant Improvement for Some Patients with Melanoma

Novel Drug Combo Induces Encouraging Results in Patients With Heavily Pretreated Breast Cancer

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