Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

1. Patients who had never previously received anti-angiogenesis treatments had longer progression-free survival

2. Adverse events of combination avelumab and axitinib are mild and include abdominal pain, diarrhea, nausea, and vomiting.

Evidence Rating Level: 2 (Good)

Study Rundown:

Type B3 thymoma and thymic carcinoma are aggressive tumours with poor survivability outcomes and there are not many treatment options available for advanced or metastatic disease. This study investigated the efficacy and safety of avelumab and axitinib, an anti-PD-L1 inhibitor and an anti-angiogenesis drug, respectively. The primary outcome of interest was overall response rate (ORR) and secondary outcomes included progression-free survival (PFS) and safety. The overall response rate was 34% (11 of 32 patients), but none had a complete response. There were 34% of patients who had a partial response. In 66% of patients, there was a decrease in size of tumour. Patients who had never previously received anti-angiogenesis treatment had greater ORR (47% vs. 15%). Median progression free survival was 7.5 months. PFS to 6 months was 61.3% and for 12 months was 29.0%. Patients who had never previously received anti-angiogenesis treatment had longer PFS (10.0 months vs. 4.5 months). Safety was measured through adverse events (AEs) and most patients who experienced AEs had only mild symptoms including abdominal pain, diarrhea, nausea, and vomiting. The most common severe AE was hypertension, noted in 19% of patients. Axitinib dose reductions were required in 25% of patients due to AEs. There were no treatment related deaths. Limitations to this study include small study size, which limits the interpretation of subgroup analyses. Additionally, late-onset AEs may not be appreciable in this follow-up timeframe. Despite attention to safety parameters of this treatment, it is difficult to assess impacts on health-related quality of life. Overall, the results from this study suggest that there may be benefit of avelumab and axitinib as second-line treatment after standard platinum-based chemotherapy treatment of advanced and metastatic type B3 thymoma and thymic carcinoma.

Relevant Reading: Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma

In-Depth [randomized controlled trial]:

This single arm, phase 2 trial was completed out of 2 healthcare centres in Italy. The study enrolled 32 adult patients with type B3 thymoma or thymic carcinoma whose disease had progressed despite standard treatment chemotherapy. The ORR was 34% (90% confidence interval (CI), 21-50%). In 26 patients with enough tumour burden to obtain a sample, a subgroup analyses of high, low, or negative PD-L1 tumour expression showed similar ORR between the subgroups (38%, 33%, and 28% respectively). The ORR was 47% (90% CI, 27-68%) in 19 patients who had not previously received anti-angiogenesis agents as compared to 15% in 13 patients who had previously received anti-angiogenesis treatment (90% CI, 3-41%). The median duration of follow-up for PFS was 22.4 months. Median PFS was 7.5 months (90% CI, 3.7-10.0 months) while 6-month PFS was 61.3% (90% CI,45.3-73.9%) and for 12-months it was 29.0% (90% CI, 16.0-43.4%). Post-hoc subgroup analysis of patients who had not previously received treatment with anti-angiogenesis agents showed a median PFS of 10.0 months (90% CI, 7.4-13.1 months) as compared to 4.5 months for those who had (90% CI, 2.4-7.5 months; hazard ratio (HR) 0.56, 90% CI, 0.28-1.09). PFS was not associated with PD-L1 expression when patients were grouped according to low expression vs. high expression or negative status (PFS HR, 1.07; 90% CI 0.51-2.26).

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