Southeastern Medical Oncology Center

Desmoplastic melanoma is a distinct subtype of melanoma known to have preexisting immune infiltrates and high ultraviolet light damage, resulting in a high tumor mutational burden. We hypothesized that this may result in high response rates with single-agent anti-programmed death protein 1 (PD-1) therapy. SWOG S1512 was a two-cohort clinical trial testing the activity of pembrolizumab in patients with surgically resectable (cohort A) and unresectable (cohort B) desmoplastic melanoma. Here we report on the cohort B single-arm clinical trial, which enrolled 27 patients with unresectable desmoplastic melanoma receiving pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years, with the primary endpoint of complete response rate. The complete response rate was 37% (95% confidence interval: 19-58%), and the post hoc endpoint of objective response rate was 89% (95% confidence interval: 71-98%). The estimated secondary endpoints of 3-year melanoma-specific progression-free survival and overall survival were 84% and 96%, respectively, with only one patient having died from melanoma progression. Ten patients (37%) experienced grade 3 or 4 adverse events, and nine patients (33%) discontinued treatment because of adverse events. Patients with advanced desmoplastic melanoma have a high response rate to single-agent PD-1 blockade therapy, supporting single-agent anti-PD-1 as the treatment of choice, but are limited by a frequency of toxicities that is numerically higher than in other patient populations. ClinicalTrials.gov identifier: NCT02775851.

In patients with cancer who have venous thromboembolism (VTE) events, long-term anticoagulation with low-molecular-weight heparin (LMWH) is recommended to prevent recurrent VTE. The effectiveness of a direct oral anticoagulant (DOAC) compared with LMWH for preventing recurrent VTE in patients with cancer is uncertain.

To evaluate DOACs, compared with LMWH, for preventing recurrent VTE and for rates of bleeding in patients with cancer following an initial VTE event.

Unblinded, comparative effectiveness, noninferiority randomized clinical trial conducted at 67 oncology practices in the US that enrolled 671 patients with cancer (any invasive solid tumor, lymphoma, multiple myeloma, or chronic lymphocytic leukemia) who had a new clinical or radiological diagnosis of VTE. Enrollment occurred from December 2016 to April 2020. Final follow-up was in November 2020.

Participants were randomized in a 1:1 ratio to either a DOAC (n = 335) or LMWH (n = 336) and were followed up for 6 months or until death. Physicians and patients selected any DOAC or any LMWH (or fondaparinux) and physicians selected drug doses.

The primary outcome was the recurrent VTE rate at 6 months. Noninferiority of anticoagulation with a DOAC vs LMWH was defined by the upper limit of the 1-sided 95% CI for the difference of a DOAC relative to LMWH of less than 3% in the randomized cohort that received at least 1 dose of assigned treatment. The 6 prespecified secondary outcomes included major bleeding, which was assessed using a 2.5% noninferiority margin.

Between December 2016 and April 2020, 671 participants were randomized and 638 (95%) completed the trial (median age, 64 years; 353 women [55%]). Among those randomized to a DOAC, 330 received at least 1 dose. Among those randomized to LMWH, 308 received at least 1 dose. Rates of recurrent VTE were 6.1% in the DOAC group and 8.8% in the LMWH group (difference, -2.7%; 1-sided 95% CI, -100% to 0.7%) consistent with the prespecified noninferiority criterion. Of 6 prespecified secondary outcomes, none were statistically significant. Major bleeding occurred in 5.2% of participants in the DOAC group and 5.6% in the LMWH group (difference, -0.4%; 1-sided 95% CI, -100% to 2.5%) and did not meet the noninferiority criterion. Severe adverse events occurred in 33.8% of participants in the DOAC group and 35.1% in the LMWH group. The most common serious adverse events were anemia and death.

Among adults with cancer and VTE, DOACs were noninferior to LMWH for preventing recurrent VTE over 6-month follow-up. These findings support use of a DOAC to prevent recurrent VTE in patients with cancer.

ClinicalTrials.gov Identifier: NCT02744092.