Triplet Shows Promise in Pediatric Kaposi Sarcoma

Investigators working in Malawi found an association between the combination of vincristine, bleomycin, and etoposide (VBE) and improved quality of life (QoL), overall survival (OS), and event-free survival (EFS) in children with Kaposi sarcoma (KS).

A total of 56 patients were included in the analysis and 34 children (60.1%) completed all 6 cycles of treatment. Using the Lansky score to assess pre- and posttreatment QoL, 80% (n = 45) of patients reported higher QoL posttreatment. QoL was unchanged for 18% of patients, and 2% of patients reported poorer QoL.

At 12 months, OS was 71% (95% CI, 56-82) and retention, defined as the number children remaining after excluding for death and default, was 60% (95% CI, 45-71). EFS was 50% (95% CI, 36-63). At 24 months’ follow-up, OS was 59% (95% CI, 44-72).

“This study shows that a combination regimen of VBE for treatment of childhood KS in resource-limited settings may improve survival, response to treatment, and quality of life, but numbers were inadequate to confirm significant improvement,” the investigators wrote. “Larger clinical trials of this and other chemotherapy options in pediatric populations would validate treatment guidance.”

KS is an aggressive, multifocal disease arising from vascular and lymphatic endothelial cells involving the skin and visceral organs. It is the second most frequently diagnosed HIV-related malignancy worldwide and the second most common pediatric tumor in sub-Saharan Africa, where HIV and human herpesvirus 8 are endemic. Neither HIV nor widespread KS are curable and treatment is aimed at disease reduction and improving QoL.

Antiretroviral therapy (ART) is the first-line treatment for AIDS-related KS. ART alone may cause long-term regression of lesions and localized lymphadenopathy, and patients with extensive skin involvement and disseminated or systemic disease also receive systemic chemotherapy. Adult guidelines recommend first-line usage of liposomal doxorubicin, which is expensive and difficult to obtain in low-income countries.

There are no data supporting the use of first-line liposomal doxorubicin in children. Furthermore, there are no standard staging criteria or treatment regimens for pediatric KS.

A study of Zimbabwean adults with KS showed that oral etoposide was associated with improved QoL with better psychological outcomes, less social disruption, and fewer side effects than supportive care alone, radiotherapy, or a 3-drug combination of actinomycin-D, vincristine, and bleomycin.

Based on those results, investigators hypothesized that the oral antiangiogenic etoposide took several weeks to be effective, while the vincristine/bleomycin combination worked more quickly. From August 2012 to March 2015, investigators treated Malawian children with KS at the Queen Elizabeth Central Hospital with VBE in an attempt to improve survival. Some patients with treatment failure despite several courses of therapy also received thalidomide.

The median age was 8 years (interquartile range [IQR], 3-12). Forty-eight children (86%) had HIV infection, and 36 (77%) of those patients had received ART for a median duration of 10 months (IQR, 1.6-23.5). Twelve ART-naïve children (23%) commenced ART as soon as possible after diagnosis. The median length of symptoms was 6 months (IQR, 1-12) and most children (93%) presented with a combination of skin lesions.

All eight HIV-negative children (14%) presented with generalized (n = 5) or localized (n = 3) lymphadenopathy.

Eighteen children (32%) had complete response to treatment. Twelve (21%) had partial response, defined as >50% reduction in size of sentinel lesion. Three patients (5%) had stable disease and 7 (12.5%) had no response or disease progression.

The risk for death was 26.4% (95% CI, 16-39) and 13.4% (95% CI 6-24) for default at 12 months. The risk for death at 24 months was 36.1% (95% CI, 24-49) and 21.1% (95% CI, 11-33) for default.

On multivariate analysis, investigators found that only high numbers of treatments were significantly associated with a protective effect from death, loss to follow-up, or an event (hazard ratio [HR] 0.45; 95% CI, 0.30-0.69). For children who completed treatment, previous treatment for tuberculosis was associated with an increased risk for attrition (HR, 3.47; 95% CI, 0.94-12.75).

Macken M, Dale H, Moyo D, et al. Triple therapy of vincristine, bleomycin, and etoposide for children with Kaposi Sarcoma: Results of a study in Malawian children [published online October 8, 2017]. Pediatr Blood Cancer. doi: 10.1002/pbc.26841.