Avelumab Shows ‘Encouraging’ Activity For Heavily Pretreated Ovarian Cancer

Preliminary research suggests that the PD-L1 inhibitor avelumab may have efficacy in the setting of recurrent or refractory ovarian carcinoma

medwireNews: The programmed cell death ligand 1 (PD-L1) inhibitor avelumab has shown antitumour activity among patients with heavily pretreated advanced ovarian cancer, report the JAVELIN Solid Tumor trial investigators. 

“[O]ur data provide the rationale for further studies of avelumab in ovarian cancer”, the team writes in JAMA Oncology. The researchers have previously reported results for the phase Ib study including for a cohort of patients with non-small-cell lung cancer .  

As part of the JAVELIN Solid Tumor trial, the investigators recruited 125 women with stage III or IV epithelial ovarian, fallopian tube or peritoneal cancer who had received a median of three prior lines of treatment, and had disease that was recurrent or refractory to platinum-based chemotherapy. 

Patients received avelumab 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity, with a median treatment period of 2.8 months, explain Mary Disis, from the University of Washington in Seattle, USA, and co-workers. 

After a median 26.6 months of follow-up, 9.6% of the patients achieved a confirmed objective response, including a complete response in 0.8% and a partial response in 8.8%, while 42.4% had stable disease.  

The objective response rate (ORR) was highest among the patients with no more than one prior line of therapy for locally advanced or metastatic disease, at 21.1%, falling to 7.4% for those with three or more previous lines of treatment. And the ORR was higher for patients who achieved a complete or partial response after their last platinum-based regimen than those whose best response had been stable disease (13.6 vs 5.3%). 

The ORR was 7.9% for the 38 patients whose tumours tested negative for PD-L1 using a threshold of 1%, rising to 11.8% for the 76 patients with PD-L1-positive tumours. When the threshold was raised to 5% positivity, the ORRs were 9.8% and 12.5%, respectively. 

Median progression-free and overall survival times for the whole cohort were 2.6 and 11.2 months, respectively, with corresponding 1-year rates of 10.2% and 47.0%.  

Avelumab had an “acceptable safety profile”, the investigators report, with grade 3 or 4 treatment-related adverse events (AEs) occurring in 7.2% of patients, but lipase elevation was the only grade 3 AE to occur in more than one individual (2.4%). 

Immune-related AEs occurred in 16.8% of the group, most commonly hypothyroidism, and there were three grade 3 AEs – individual cases of colitis, type 2 diabetes and myositis. 

“We were unable to draw conclusions about whether response was more likely in patients with immune-related AEs because of the small number of patients and the confounding effects of treatment duration”, comment Mary Disis et al.

The investigators note that the phase III JAVELIN Ovarian 100 and JAVELIN Ovarian 200 trials have begun to assess the efficacy of avelumab in combination with carboplatin plus paclitaxel, and pegylated liposomal doxorubicin, respectively. 

In addition, early trials, such as JAVELIN PARP Medley, are investigating checkpoint inhibitor efficacy in combination with PARP inhibitors for patients with platinum-sensitive ovarian cancer, they say. 

“Results from these ongoing studies will help to define an appropriate role for checkpoint inhibitors within the treatment of ovarian cancer”, the team concludes. 

 

Reference 

Disis ML, Taylor MH, Kelly K, et al. Efficacy and safety of avelumab for patients with recurrent or refractory ovarian cancer. Phase 1b results from the JAVELIN Solid Tumor t rial . JAMA Oncol; Advance online publication 24 January 2019. doi:10.1001/jamaoncol.2018.6258

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