Treatment with avelumab, either alone or in combination, did not improve survival over standard therapy in patients with platinum-resistant or -refractory ovarian cancer, according to study results published in The Lancet Oncology.
In the JAVELIN Ovarian 200 trial (ClinicalTrials.gov Identifier: NCT02580058), researchers compared avelumab monotherapy, avelumab in combination with pegylated liposomal doxorubicin (PLD), and PLD alone.
The study enrolled 566 patients from 24 countries. Most patients (69%) had high-grade serous histology, and 13% had clear cell histology. At baseline, 48% had primary resistant disease, 37% had bulky disease, and 25% had platinum-refractory disease.
The patients were randomly assigned to receive avelumab alone (n=188), avelumab plus PLD (n=188), or PLD alone (n=190). The primary endpoints included progression-free survival (PFS) and overall survival (OS).
The median treatment duration was 16.0 weeks in the PLD arm and 10.1 weeks in the avelumab monotherapy arm. In the combination arm, the median treatment duration was 16.9 weeks for avelumab and 16.3 weeks for PLD.
The median PFS by blinded independent central review was 3.5 months in the PLD arm, 1.9 months in the avelumab arm, and 3.7 months in the combination arm.
For combination treatment compared with PLD, the stratified hazard ratio (HR) for PFS was 0.78 (repeated 93.1% CI, 0.59-1.24; one-sided P =.030). For avelumab compared with PLD, the stratified HR for PFS was 1.68 (93.1% CI, 1.32-2.60; one-sided P >.99).
The median OS was 13.1 months in the PLD arm, 11.8 months in the avelumab arm, and 15.7 months in the combination arm.
For the combination compared with PLD, the stratified HR for OS was 0.89 (repeated 88.85% CI, 0.74-1.24: one-sided P =.21). For avelumab compared with PLD, the stratified HR for OS was 1.14 (88.85% CI, 0.95-1.58; one-sided P =.83).
The most common grade 3 or higher treatment-related adverse events (TRAEs) were:
- Palmar-plantar erythrodysesthesia syndrome (10% in the combination arm, 5% in the PLD arm, and none in the avelumab arm)
- Rash (6%, 2%, and none, respectively)
- Fatigue (5%, 2%, and none, respectively)
- Stomatitis (5%, 3%, and none, respectively)
- Anemia (3%, 5%, and 2%, respectively)
- Neutropenia (5%, 5%, and none, respectively)
- Neutrophil count decrease (5%, 4%, and none, respectively).
Serious TRAEs were observed in 18% of patients in the combination arm, 11% in the PLD arm, and 7% in the avelumab arm. TRAEs proved fatal in 1 patient in the PLD arm (sepsis) and 1 in the avelumab arm (intestinal obstruction).
“Although the JAVELIN Ovarian 200 trial did not show a significant progression-free survival or overall survival benefit in the overall population, results from this trial provide insights for patient selection in future studies of immune checkpoint inhibitors in the treatment of platinum-resistant or platinum-refractory ovarian cancer,” the study authors wrote.
Disclosures: This research was supported by Pfizer and Merck. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Pujade-Lauraine E, Fujiwara K, Ledermann JA, et al. Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum-resistant or platinum-refractory ovarian cancer (JAVELIN Ovarian 200): an open-label, three-arm, randomised, phase 3 study. Lancet Oncol. 2021;22(7):1034-1046. doi:10.1016/S1470-2045(21)00216-3