Systematic review and meta-analysis efficacy and safety of immune checkpoint inhibitors in advanced melanoma patients with anti-PD-1 progression: a systematic review and meta-analysis

Background More than half of melanoma patients taking first-line anti-PD-1 therapy either express transient or no response at all. The efficacy and safety of secondary treatments for these patients are still not well established. Here, we evaluate the efficacy and safety of different melanoma FDA-approved ICI modalities used in post-anti-PD-1 refractory settings. Materials and methods We searched the PubMed database and the ASCO meetings library for studies on advanced melanoma patients with cancer progression on anti-PD-1 therapy and were then treated with ipilimumab, nivolumab/ipilimumab combination, or retreated with anti-PD-1. Primary and secondary endpoints were efficacy and toxicity, respectively. Pooled estimates for each treatment group were obtained using a random or fixed effects model according to detected heterogeneity. Results Fourteen studies, of which 10 on ipilimumab, 2 on anti-PD-1 treatment, and 6 on combination therapies, were included, involving a total of 1460 patients. Twelve studies reported objective response rates (ORRs) and nine of them reported immune-related adverse events (irAEs). As for ORR, patients experienced a response that was inferior compared to the same therapy in treatment -naïve patients, with combination therapy having the best ORR of a pooled 23.08% (95% CI: 16.75% to 30.03%), followed by ipilimumab with a pooled ORR of 8.19% (95% CI: 5.78% to 10.92%). Survival data were also inferior in the ipilimumab cohort (mOS: 5.1 to 7.4 months) compared to ipilimumab in anti-PD-1 naive patients. As for grade 3/4 irAE occurrence, the ipilimumab cohort showed an estimate of 43.77% (95% CI 22.55% to 66.19%) (AU)

Systematic review and meta-analysis efficacy and safety of immune checkpoint inhibitors in advanced melanoma patients with anti-PD-1 progression: a systematic review and meta-analysis.

BACKGROUND: More than half of melanoma patients taking first-line anti-PD-1 therapy either express transient or no response at all. The efficacy and safety of secondary treatments for these patients are still not well established. Here, we evaluate the efficacy and safety of different melanoma FDA-approved ICI modalities used in post-anti-PD-1 refractory settings. MATERIALS AND METHODS: We searched the PubMed database and the ASCO meetings library for studies on advanced melanoma patients with cancer progression on anti-PD-1 therapy and were then treated with ipilimumab, nivolumab/ipilimumab combination, or retreated with anti-PD-1. Primary and secondary endpoints were efficacy and toxicity, respectively. Pooled estimates for each treatment group were obtained using a random or fixed effects model according to detected heterogeneity. RESULTS: Fourteen studies, of which 10 on ipilimumab, 2 on anti-PD-1 treatment, and 6 on combination therapies, were included, involving a total of 1460 patients. Twelve studies reported objective response rates (ORRs) and nine of them reported immune-related adverse events (irAEs). As for ORR, patients experienced a response that was inferior compared to the same therapy in treatment -naïve patients, with combination therapy having the best ORR of a pooled 23.08% (95% CI: 16.75% to 30.03%), followed by ipilimumab with a pooled ORR of 8.19% (95% CI: 5.78% to 10.92%). Survival data were also inferior in the ipilimumab cohort (mOS: 5.1 to 7.4 months) compared to ipilimumab in anti-PD-1 naive patients. As for grade 3/4 irAE occurrence, the ipilimumab cohort showed an estimate of 43.77% (95% CI 22.55% to 66.19%). CONCLUSION: Our findings provide the best current evidence that patients who progress on anti-PD-1 can still respond to different ICI modalities (ipilimumab with or without nivolumab, and retreatment or continuation beyond progression with anti-PD-1) with tolerable grade 3/4 irAEs. However, more prospective clinical trials are needed to confirm these results.

Field and laboratory testing in young elite soccer players.

AIM: To determine if there are correlations between the physical fitness of young soccer players assessed by field and laboratory testing. METHODS: Thirty four male soccer players took part in the study (mean (SD) age 17.5 (1.1) years, height 177.8 (6.7) cm, weight 70.5 (6.4) kg). Maximal oxygen uptake (VO(2)MAX) during treadmill running and vertical jump height on a force platform were measured in the laboratory. Field tests consisted of a soccer specific endurance test (Bangsbo test) and 30 m sprint with 10 m lap times. RESULTS: The Bangsbo test correlated with the lowest velocity associated with VO(2)MAX (vVO(2)MAX; R(2) = 0.55, p<0.001), but not with VO(2)MAX. Sprint times at 30 m and 20 m were related to peak extension velocity and peak extension force measured during vertical jumping, but not to vertical jump height per se. The jumping force and velocity could explain 46% of the 30 m sprint performance (R(2) = 0.46, p<0.001). CONCLUSION: The Bangsbo test and 30 m sprint test correlate with vVO(2)MAX and vertical jump force and velocity respectively. The Bangsbo test does not give a good estimate of VO(2)MAX in young soccer players.

Evaluation of the results of intraocular lens implantation in Egyptian children.

A retrospective study was done for 95 eyes of Egyptian children in whom I.O.L. implantation was performed between 1985 and 1986 to treat unilateral cataract due to trauma or congenital or aphakia. The average range of follow up period was three to four years old. It was revealed that I.O.L. In traumatic cataract gave the best results (as regards the visual acuity with minimal complications) especially with anterior chamber lenses and still the secondary implantation of A.C. lenses had to some extent better results than that of primary A.C. lenses. In congenital cataract, P.C. lenses gave the worst results. Again, the older the age of the children, the better the results of I.O.L. implantation.

Pars plana versus limbal lensectomy in soft cataract.

With the use of automated vitrectomy instruments a new dimension has been added to the treatment of soft cataracts. Surgical approach through the limbus and pars plicata has been described previously. This work is to compare the results of both surgical techniques. Twenty eyes of soft cataract underwent lensectomy and vitrectomy using the vitrophage. Pars plana approach was applied to 10 eyes, while limbal approach was applied to the rest of the cases. No major preoperative or postoperative complication were encountered in both techniques in a follow up period up to 12 months. However, pars plana lensectomy and vitrectomy offers many advantages over the limbal one with minimal complications.