ABSTRACT
Background: Patients(pts) with metastatic acral melanoma respond poorly to anti-PD-1 monotherapy. Apatinib, a vascular endothelial growth factor (VEGF) inhibitor, is a kind of antiangiogenic drugs which have shown synergistic therapeutic effects in combination with PD-1 blockade. We conducted this single-center, open label phase trial to evaluate the safety and efficacy of camrelizumab in combination with apatinib in advanced treatment-naïve acral melanoma pts. Methods: Eligible participants were adult pts (aged 18 to 75) with histologically confirmed unresectable stage or distant metastatic acral melanoma. Exclusion criterion included unknown primary melanoma, brain metastatic disease or previous use of anti PD-1 ab. Pts received camrelizumab at 200mg intravenous infusion every 2 weeks, in combination with apatinib 250 mg orally once a day. The primary endpoint was ORR according to RECIST 1.1 criteria, and the secondary endpoints were safety and RFS. Results: Thirty pts were enrolled from April 2019 to January 2021. Basic characteristics: the mean age was 56.7 years, 22 pts were at stage, 33.3% had an elevated LDH level. Median tumor burden was 45mm (10-187). Gene mutation: Nras 4, cKit 3, Braf 2. Up to January 2021, 27 pts could be evaluated, in which 2 pts got CR, 4 pts achieved PR, and 63% experienced tumor shrinkage. The ORR and DCR were 22.2% and 77.8%, respectively. With a median follow up time of 8.3 months, the median PFS was 8.0 months (95% CI, 3.68, 10.19), the one-year durable response rate was 83.3% and the duration of response time was still not reached. Univariate analysis showed high LDH level was negatively associated with PFS. Whole exome data of baseline tumor biopsies revealed a positive correlation between high copy number variation (CNV) plus high mutational load (TMB) and efficacy, and all of the 4pts with MDC1 gene mutation got tumor shrink and 2 got PR. 96.7% pts experienced treatment-related AEs (TRAEs), including hand foot syndrome in 40%, proteinuria in 40%, liver dysfunction in 36.7%, and hypothyroidism in 30%. The grade 3-4 TRAEs were 33.3%. AE-related permanent discontinuation occurred in only 13.3% pts. 6 pts had delays of treatment due to the COVID-19 epidemic. No dose-limiting toxicities and suspected unexpected AEs were observed in the combination. Conclusions: The combination of apatinib plus camrelizumab was tolerable and showed promising antitumor activities and PFS improvement in pts with treatment-naïve metastatic acral melanoma. The survival is still in follow up.
ABSTRACT
As the ongoing COVID-19 pandemic disrupts established daily routines, it underlines the role that families play in redefining social order and reorganizing people's economic and social lives. In this paper, we investigate methods that Chinese and South Korean families have adopted to cope with the rapid changes brought on by the COVID-19 pandemic. We emphasize families' responses to sudden changes in three domains: education and home schooling, economic downturn and unemployment, and mental health challenges. By integrating online education and remote working into a new form of family life and sharing economic and emotional risks among members, families shape social order during a period of unprecedented uncertainty. We highlight the fact that family members experience intensified work-family or school-family conflicts. Disadvantaged families are the most severely affected, as they are at high risk of job loss and lack proper protections. The absence of institutional protections and interventions has created further economic and emotional hardships for these vulnerable families. Informal and nonregular workers require more stable labor market conditions for the well-being of their families. Future research may include a systematic data collection and analysis of disadvantaged families, as this would offer a better understanding of the challenges and untenable choices that families face during times of crisis.