Toronto, Canada—Combining durvalumab with pegylated liposomal doxorubin (PLD) has shown a tolerable safety profile and promising efficacy in patients with platinum-resistant recurrent ovarian cancer, according to data prepared for presentation at the 2020 SGO Annual Meeting on Women’s Cancer.

These findings were gleaned from a phase 1/2, multi-center study by Roisin Eilish O'Cearbhaill, MD, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, and colleagues in which the efficacy and safety of durvalumab plus PLD were assessed and genomic characteristics tied to response and progression-free survival (PFS) were identified.

According to the investigators, PLD has a 6-month PFS (PFS6) of 25%; thus, they examined the null hypothesis of PFS6 ≤25% against the alternative hypothesis at 0.05 level using 90% 2-sided CI.

With phase 1 results regarding PFS6 previously reported, Dr O'Cearbhaill et al focused here on phase 2, which comprised 40 patients (median age, 65 years years) given at least 1 dose of PLD 40 mg/m² plus durvalumab 1500 mg every 4 weeks.

The response rate was 22.5% (90% CI, 10.8-38.5), including 4 complete responses and 5 partial responses, and the median PFS was 5.5 months; the median overall survival was 17.6 months.

Treatment-related adverse events of grade ≥3 occurring in ≥2 patients were palmar-plantar erythrodysesthesia syndrome/rash (27.5%), stomatitis (10%), lymph count decrease (10%), lipase increase (5%), and anemia (5%).

From exom sequencing data available for 28 patients, it was observed that no patients had BRCA1/BRCA2 mutations, and 3 patients had hypermutated non-MSI phenotypes. An evaluation of copy numbers yielded multiple potential mechanisms for resistance to the combination therapy.

Previously, deletions of LRP1B were shown to drive PLD resistance. Here, Dr O'Cearbhaill also found that PFS (P = .0016) negatively correlated with LRP1B deletions among recipients of durvalumab plus PLD.

Patients with MYC amplifications receiving the combination therapy also had fewer responses (P = .0005) and shorter PFS (P = .006; hazard ratio, 2.889).

Ultimately, adding durvalumab to PLD yielded a tolerable safety profile and showed promising efficacy in patients with platinum-resistant recurrent ovarian cancer.

“The study met its primary endpoint with improvement in PFS6. We confirm the negative impact of LRP1B deletions on PLD-based therapies,” Dr O'Cearbhaill and colleagues concluded.

“MYC amplification may be central in driving resistance to the combination and has not been previously linked to PLD efficacy,” they added.—Hina Porcelli

O'Cearbhaill RE, Homicsko K, Wolfer A, et al. A phase I/II study of chemo-immunotherapy with durvalumab (durva) and pegylated liposomal doxorubicin (PLD) in platinum-resistant recurrent ovarian cancer (PROC): Genomic sequencing and updated efficacy results. Presented at: the 2020 SGO Annual Meeting on Women’s Cancer; March 28-31, 2020; Toronta, Canada. Abstract 51.