RESUMO
BACKGROUND & AIMS: Prospective data on treatment after immune checkpoint inhibitor (ICI) therapy in hepatocellular carcinoma (HCC) are lacking. We conducted a phase II multicentre study on cabozantinib after ICI treatment in HCC. METHODS: This is an investigator-initiated, single-arm, clinical trial involving academic centres in Hong Kong and Korea. Key eligibility criteria included diagnosis of HCC, refractoriness to prior ICI-based treatment, and Child-Pugh A liver function. A maximum of two prior lines of therapy were allowed. All patients were commenced on cabozantinib at 60 mg/day. The primary endpoint was progression-free survival (PFS). RESULTS: Forty-seven patients were recruited from Oct 2020 to May 2022; 27 and 20 patients had received one and two prior therapies, respectively. Median follow-up was 11.2 months. The median PFS was 4.1 months (95% CI 3.3-5.3). The median overall survival (OS) was 9.9 months (95% CI 7.3-14.4), and the 1-year OS rate was 45.3%. Partial response and stable disease occurred in 3 (6.4%) and 36 (76.6%) patients, respectively. When used as a second-line treatment (n = 27), cabozantinib was associated with a median PFS and OS of 4.3 (95% CI 3.3-6.7) and 14.3 (95% CI 8.9-NR) months, respectively. The corresponding median PFS and OS were 4.3 (95% CI 3.3-11.0) and 14.3 (95% CI 9.0-NR) months, respectively, for those receiving ICI-based regimens with proven benefits (n = 17). The most common grade 3-4 treatment-related adverse event was thrombocytopenia (6.4%). The median dose of cabozantinib was 40 mg/day. The number of prior therapies was an independent prognosticator (one vs. two; hazard ratio = 0.37; p = 0.03). CONCLUSIONS: Cabozantinib demonstrated efficacy in patients who had received prior ICI regimens; survival data for second-line cabozantinib following first-line ICI regimens provide a reference for future clinical trial design. The number of prior lines of treatment may be considered a stratification factor in randomised studies. IMPACT AND IMPLICATIONS: Prospective data on systemic treatment following prior immune checkpoint inhibitor (ICI) therapy for hepatocellular carcinoma (HCC) are lacking. This phase II clinical trial provides efficacy and safety data on cabozantinib in patients who had received prior ICI-based treatment. Exploratory analyses showed that the performance of cabozantinib differed significantly when used as a second- or third-line treatment. The above data could be used as a reference for clinical practice and the design of future clinical trials on subsequent treatment lines following ICIs. GOV IDENTIFIER: NCT04588051.
RESUMO
BACKGROUND: Platelet-rich plasma (PRP) injections have been introduced to augment the recovery of patients with shoulder pathology. Although multiple studies have been published, no large-scale trials or meta-analyses have assessed the efficacy of nonoperative shoulder PRP injection. OBJECTIVE: To assess the efficacy of nonoperative PRP shoulder injection in rotator cuff pathology for pain as measured by the visual analog scale (VAS) and range of motion (ROM). DESIGN: Two authors independently screened the Medline and Cochrane databases to include prospective studies that reported VAS and ROM outcomes for nonoperative shoulder PRP injections for rotator cuff pathology. Study quality was assessed using the revised Cochrane Collaboration risk-of-bias tool and modified Downs and Black checklist. Subsequent meta-analysis was performed to determine the effect of nonoperative PRP injections on pain and ROM 3 to 12 months after intervention. RESULTS: Six studies met systematic review criteria. The included studies used different PRP formulations (concentration, leukocyte count), injection protocols (approach, injection number), and varied study designs. Three studies concluded that PRP provided no significant benefit for pain and ROM when compared to physical therapy. Within-group meta-analysis of six fairly heterogeneous studies (I2 77.8%) demonstrated a statistically significant (P < .001) improvement in pain 3 to 12 months after PRP injection. Within-group meta-analysis for four studies for shoulder flexion and abduction was found to be too heterogeneous to derive meaningful results. CONCLUSION: There is a limited quantity of high-quality studies that assess the efficacy of nonoperative PRP shoulder injection for pain and ROM. Systematic review of PRP injections did not demonstrate an improvement in pain or ROM compared to physical therapy. Although within-group meta-analysis of nonoperative PRP statistically showed that nonoperative PRP improved pain, the lack of adequate negative controls precludes the ability to conclude whether improvements were due to natural recovery or nonoperative PRP.