Corneal Perforation in a Patient Treated with Atezolizumab-Bevacizumab Combination Therapy for Unresectable Hepatocellular Carcinoma.

BACKGROUND Immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1 (PD-1), or its ligand PD-L1, are the mainstay treatment for several metastatic malignant conditions. ICIs are associated with multiple toxic adverse events affecting various organs, known collectively as immune-related adverse events (irAEs). Dry eye, uveitis, ocular myasthenia, and cicatrizing conjunctivitis are well-recognized ocular irAEs associated with ICIs. CASE REPORT We present a case of 69-year-old man who presented with paracentral, punch-out corneal perforation in the left eye, associated with bilateral severe ocular surface disease 3 weeks after receiving the second dose of atezolizumab-bevacizumab combination therapy for the treatment of unresectable hepatocellular carcinoma. Corneal gluing using cyanoacrylate glue was performed along with bandage contact lens application and temporary tarsorrhaphy to seal the corneal perforation and improve the ocular surface. On the subsequent follow-ups, the corneal glue was unstable and dislodged. Thus, penetrating keratoplasty was performed to salvage the globe along with holding the combination therapy. At the 8-month follow-up, the graft remained clear, and the ocular surface improved substantially in both eyes. CONCLUSIONS Ocular irAEs associated with immune-modulating agents can lead to vision-threatening complications. Therefore, communications between oncologists and ophthalmologists in a multidisciplinary team would be of utmost importance for early detection and timely management of any ocular-related adverse events associated with the use of immunotherapy agents.

Evolution in sites of recurrence over time in breast cancer patients treated with adjuvant endocrine therapy.

BACKGROUND: Hormone receptor positive breast cancer is characterized by a prolonged risk of recurrence. Extended adjuvant endocrine therapy improves disease-free survival (DFS), but no effect on overall survival has been observed. This may be explained by changes in the relative contribution of local, regional and distant recurrences as well as non-breast cancer death to DFS events over time. PATIENTS AND METHODS: We reviewed sequential reports of large, randomized, adjuvant endocrine therapy trials extracting the number and types of recurrences defining DFS events at each point over follow-up. Meta-regression was performed to explore the relative contribution of contralateral, loco-regional and distant recurrences as well as non-breast cancer death to DFS over time. RESULTS: Analysis included 17 reports of 6 trials reporting outcomes between 28 and 120 months of follow-up. Over time, there was increasing contribution of contralateral breast cancer (5% of events at 20 months to 12% at 120 months; ß = 0.663, p = 0.004) and non-breast cancer death (20% of events at 20 months to 32% at 120 months; ß = 0.581, p = 0.01). There was a non-significant reduction in the contribution of distant recurrence (57% of events at 20 months to 45% at 120 months; ß = -0.397, p = 0.11), but no change in loco-regional recurrence (18% of events at 20 months to 11% at 120 months; ß = -0.301, p = 0.30). CONCLUSIONS: With increasing follow-up, DFS events are increasing defined by contralateral recurrence and non-breast cancer deaths with a trend for fewer distant recurrences. This may explain the limited association between DFS and overall survival with extended adjuvant endocrine therapy.

Efficacy of extended adjuvant therapy with aromatase inhibitors in early breast cancer among common clinicopathologically-defined subgroups: A systematic review and meta-analysis.

BACKGROUND: Randomized controlled trials (RCTs) have shown improvements in breast cancer outcomes from extending treatment with aromatase inhibitors (AIs) beyond the initial 5years after diagnosis. Consistency of this effect in common clinicopathologically defined subgroups was not been reported systematically. METHODS: We identified RCTs comparing extended AIs to placebo or no treatment using a systematic search of MEDLINE and a review of abstracts from key conferences between 2013 and 2016. Hazard ratios (HRs) and 95% confidence intervals (CI) for disease-free survival (DFS) were included in a meta-analysis using generic inverse variance and random effects modelling. Pre-specified subgroups included: age (<60±5years versus ≥60±5 years), tumor size (>2cm versus ≤2cm), nodal status (positive versus negative), hormone receptor status (double versus single receptor expression) and receipt of adjuvant chemotherapy (yes versus no). RESULTS: Seven trials comprising 16,349 patients were analyzed. Overall, the effect of extended AIs was similar in all subgroups. Non-significantly greater effect sizes were seen in patients with larger tumors (HR for DFS 0.77 versus 0.88, p for difference=0.44), nodal involvement (HR=0.72 versus 0.83, p for difference=0.22), double hormone receptor expression (HR=0.68 versus 1.01, p for difference=0.31) and receipt of adjuvant chemotherapy (HR=0.71 versus 0.80, p for difference=0.51). CONCLUSIONS: Extended treatment with AIs is associated with similar relative improvements in DFS in all subgroups analyzed. The combination of greater effect size and higher absolute risk of recurrence in node positive and larger tumors will likely translate to higher absolute benefits from extended AIs in these groups.