Safety and efficacy of multiple tyrosine kinase inhibitors in pediatric/adolescent and young adult patients with relapsed or refractory osteosarcomas: A single-institution retrospective analysis.

BACKGROUND: The prognosis of relapsed or refractory osteosarcoma remains poor. Recent reports have stated that molecular targeting agents, including multiple tyrosine kinase inhibitors (MTKIs), are effective against adult osteosarcoma. To determine the safety and efficacy of MTKI therapy in children, adolescents and young adults (AYAs), we conducted a retrospective study on adverse events and treatment outcomes. METHODS: We retrospectively reviewed the medical records of patients with relapsed or refractory osteosarcoma who received MTKI therapy at the Department of Pediatric Oncology, National Cancer Center Hospital, from December 2013 to May 2021. RESULTS: The study included 31 patients (15 males and 16 females) who received MTKIs, including sorafenib monotherapy (seven patients), sorafenib and everolimus (14 patients), and regorafenib monotherapy (10 patients). Their median age was 17 years (range: 11-22 years). The incidence of treatment-related grade 3 nonhematological adverse events was 14.3% in the sorafenib monotherapy group, 21.4% in the sorafenib with everolimus group, and 20.0% in the regorafenib monotherapy group. No grade 4 nonhematological adverse events were observed. The median progression-free survival (PFS) was 51 days in the sorafenib monotherapy group, 101 days in the sorafenib with everolimus group, and 167 days in the regorafenib monotherapy group. CONCLUSION: The safety profile of MTKI therapies in pediatric and AYA patients was comparable to that in adult patients. MTKI therapies, particularly regorafenib, against pediatric relapsed osteosarcoma can suppress tumor growth and prolong PFS with tolerable adverse events.

Pembrolizumab plus axitinib combination and the paradigm change in the treatment of advanced renal cell carcinoma.

Sequential administration of single targeted agents has been challenged as the dominant treatment paradigm in patients with metastatic renal cell carcinoma by improved outcomes obtained with combination regimens based on immune checkpoint inhibitors. Most patients treated with sequential monotherapy eventually develop drug resistance and succumb to progressive disease, leading to the search for therapies that would overcome drug resistance and result in a more durable treatment response. Improved outcomes have been demonstrated in Phase III trials in comparison with sunitinib for the combinations of axitinib plus pembrolizumab, axitinib plus avelumab, bevacizumab plus atezolizumab and ipilimumab plus nivolumab. A statistically significant improvement of both progression-free and overall survival has been demonstrated for the axitinib plus pembrolizumab combination.

The Efficacy and Safety of the Shouzu Ning Decoction Treatment Versus Halometasone Plus Celecoxib Treatment in Patients With Grade 2 HFSR: A Randomized Clinical Trial.

OBJECTIVES: To compare the effects of the Shouzu Ning Decoction (SND) and Halometasone plus Celecoxib (Hal/Cxb) as therapy in patients with grade 2 hand-foot skin reaction (HFSR). MATERIALS AND METHODS: Fifty patients with grade 2 HFSR participated in a randomized, single-center, open-label study. Patients were randomly assigned in a 1:1 ratio to receive the SND or Hal/Cxb treatment, twice daily for 4 weeks, followed by 4 weeks of post-treatment follow-up. The primary endpoint was clinical remission of HFSR at the end of the fourth week (W4). The secondary endpoints were recurrence rate, quality of life (QoL), pain intensity, and safety. RESULTS: In this study, 46 patients successfully completed the study, and 4 patients were excluded. There was no statistically significant difference between the 2 groups on demographic and baseline clinical characteristics. In the SND group, 56.52% of patients showed clinical remission at W4, which was significantly superior to that achieved in the Hal/Cxb group (26.09%, P = .036). In addition, the HF-QoL score was statistically lower in the SND group compared to the Hal/Cxb group at W2 (P = .007), W3 (P = .005), and W4 (P = .005), respectively. In line with this, the inter-group difference in NRS score was statistically significant (P = .004). CONCLUSION: In the present study, SND treatment has been observed to be effective and well tolerated for patients with grade 2 HFSR. Thus, SND treatment could be considered a suitable option for HFSR patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900027518. Registered on 17 Nov 2019.

Pembrolizumab plus axitinib for the treatment of advanced renal cell carcinoma.

Introduction: The dominant paradigm of sequential therapy of metastatic renal cell carcinoma (mRCC) with single agents has recently been challenged by improved outcomes obtained with combined regimens with immune checkpoint inhibitors. These combined regimens include the combination of pembrolizumab plus axitinib.Areas covered: Here, we provide a brief overview of the current clinical data on the pembrolizumab plus axitinib combination including mechanism of action, pharmacokinetics, efficacy and safety profile.Expert opinion: Both agents targeting the vascular endothelial growth factor (VEGF) pathway and immune checkpoint inhibitors are active as single agents in mRCC. Improved outcomes have been demonstrated in phase 3 trials in comparison with sunitinib for the combinations of axitinib plus pembrolizumab, axitinib plus avelumab, bevacizumab plus atezolizumab, and ipilimumab plus nivolumab. Among these combinations, an OS benefit has, so far, demonstrated only for the combinations of axitinib with pembrolizumab and ipilimumab with nivolumab. Although there are currently no prospective data comparing the combination of ipilimumab and nivolumab with the combination of immune checkpoint inhibitors and VEGF inhibitors, currently available retrospective analyses indicate that these two approaches achieve comparable outcomes.

Cabozantinib and nivolumab as first-line treatment in advanced renal cell carcinoma.

INTRODUCTION: In the last decade, there have been substantial changes in the management of metastatic renal cell carcinoma (mRCC) with combined regimens with immune checkpoint inhibitors (ICI) replacing targeted therapies. These combined regimens include the combination of cabozantinib plus nivolumab. AREAS COVERED: Here, we provide an overview of clinical trials evaluating the combination of cabozantinib and nivolumab and the current clinical data on mechanism of action, pharmacokinetics, efficacy, and safety profile. EXPERT OPINION: Dual immune checkpoint inhibition with nivolumab and ipilimumab as well as the combination of a vascular endothelial growth factor (VEGF) inhibitor and an immune checkpoint inhibitor have shown to improve outcomes in phase III trials in comparison to sunitinib (axitinib plus pembrolizumab, axitinib plus avelumab, bevacizumab plus atezolizumab, cabozantinib plus nivolumab, lenvatinib plus pembrolizumab). However, to date, there are no head-to-head trials comparing these new combination therapies and no biomarkers are available to guide the optimal choice of first line therapy.