Selected Articles from This Issue

Abstract

Central nervous system (CNS) metastases are a prominent cause of morbidity and mortality in patients with ALK-positive (ALK+) non-small cell lung cancer (NSCLC). ASCEND-7 was one of the first prospective studies designed to use homogenous eligibility criteria, and assessments to evaluate intra/extracranial responses and activity of an ALK targeted agent, in the presence or absence of prior treatment, in patients with ALK+ NSCLC with active brain metastases and leptomeningeal metastasis. The phase II ASCEND-7 (NCT02336451) study was designed to assess the efficacy and safety of ALK inhibitor (ALKi) ceritinib in patients with ALK+ NSCLC metastatic to the brain and/or leptomeninges. Chow and colleagues report that ceritinib showed antitumor activity in patients with ALK+ NSCLC with active CNS disease and could be considered in the management of intracranial metastasis.Results from cohort 1 of the phase II, open-label KEYNOTE-224 study demonstrated that pembrolizumab monotherapy was efficacious and tolerable in patients with advanced hepatocellular carcinoma previously treated with sorafenib. In this article, Verset and colleagues report on cohort 2 of the KEYNOTE-224 study that investigated pembrolizumab monotherapy as a therapeutic approach for patients with advanced hepatocellular carcinoma, which had not been previously treated with systemic therapy. The results showed that pembrolizumab monotherapy in this population had promising efficacy, including objective response rate with durable antitumor activity and no new safety signals. These findings support further evaluation of pembrolizumab alone or in combination with other agents for the treatment of hepatocellular carcinoma.Podoplanin (PDPN) is highly expressed in several types of tumors and is known to promote tumor growth and metastasis through binding with a C-type lectin-like receptor 2 (CLEC-2) on platelets. In osteosarcoma, PDPN-CLEC-2 binding induced PDGFs release from platelets and resulted in PDGFRs mediated growth promotion of osteosarcoma. In this study, Takemoto and colleagues developed a humanized anti-PDPN neutralizing antibody, named AP201, aiming for the clinical application for PDPN highly expressing cancer such as osteosarcoma. AP201 potently neutralized PDPN-CLEC-2 binding and inhibited tumor growth and metastasis in osteosarcoma xenograft models. Thus, targeting PDPN with a neutralizing antibody could be a novel therapeutic strategy for osteosarcoma treatment.Kaposi sarcoma (KS) remains among the most common malignancies occurring with HIV infection (HIV-KS). Oral anti-inflammatory, anti-angiogenic, and immunomodulatory agent, lenalidomide, is a potentially attractive alternative to standard chemotherapy for KS. Here, Reid and colleagues present results of a phase I/II trial to determine the maximum tolerated dose (MTD) and response rates for lenalidomide in HIV-KS. The MTD was not reached, but the authors recommended 25 mg as the phase II dose (RP2D). Reported adverse events were consistent with the established safety profile of lenalidomide and 60% of participants receiving RP2D obtained a partial response. Correlative analysis performed in a subset of participants demonstrated a significant increase in proportions of blood T cells with a regulatory phenotype, and plasma cytokines trended toward a less inflammatory pattern. Clinical response was associated with loss of KSHV transcription. Following on this study, multicenter domestic and international AIDS Malignancy Consortium trials are underway to confirm the tolerability and activity of immunomodulatory therapy in KS.