Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: Avelumab given with or without pegylated liposomal doxorubicin (PLD) does not improve survival compared with PLD alone for ovarian cancer patients with disease resistant or refractory to platinum-based chemotherapy, phase III trial findings indicate.
However, the JAVELIN Ovarian 200 investigators say their study findings may “provide insights for patient selection in future studies of immune checkpoint inhibitors” in this patient population.
The co-primary endpoint of progression-free survival (PFS) was 3.7 months for the 188 patients given avelumab 10 mg/kg every 2 weeks plus PLD 40 mg/m2 every 4 weeks and this did not significantly differ from the median PFS of 3.5 months achieved by the 190 patients given only PLD or 1.9 months for the 188 patients given only avelumab.
Similarly, median overall survival (OS) was a statistically comparable 15.7, 13.1 and 11.8 months in the three treatment arms, respectively, report Eric Pujade-Lauraine, from ARCAGY-GINECO in Paris, France, and co-authors in The Lancet Oncology.
The researchers identified some patients who may have derived greater PFS and OS benefit from avelumab plus PLD than PLD alone, namely individuals who had undergone two or three prior treatments and therefore did not have primary platinum resistance and those with tumours positive for PD-L1, CD8 or both biomarkers.
While emphasizing that these benefits were “observed in underpowered subgroup analyses, and should therefore be interpreted with caution”, the investigators recommend further research to test the hypothesis that there may be differing biological mechanisms behind primary and secondary platinum resistance.
The patients in the combination arm received a median 16.9 weeks of avelumab and 16.3 weeks of PLD therapy; the PLD-only arm received a median 16.0 weeks of treatment, whereas the avelumab-only group received treatment for a median of just 10.1 weeks.
The team reports that the most common reason for discontinuation of treatment was progressive disease and there were no new safety signals associated with avelumab given alone or in combination.
Overall, treatment-related grade 3–5 events occurred in 69% of patients given avelumab plus PLD, 59% of those given only PLD and 50% of the avelumab-only patients. The most common events of this severity included palmar–plantar erythrodysesthesia syndrome (10 vs 5 and 0%, respectively), rash (6 vs 2 and 0%), fatigue (5 vs 2 and 0%), stomatitis (5 vs 3 and 0%), anaemia (3 vs 5 and 2%), neutropenia (5 vs 5 and 0%) and neutrophil decrease (5 vs 4 and 0%).
Discussing the findings in a linked comment, Emma Barber and Daniela Matei, both from Northwestern University in Chicago, Illinois, USA, suggest that future studies of immune checkpoint blockade might improve activity in ovarian cancer by using novel combinations of immunomodulatory drugs and targeted agents.
“An alternative possibility is that immunotherapy might not be active for all patients with ovarian cancer, which means that it will be important to find biomarkers predictive of response for patient selection”, they write.
The commentators conclude: “Whether dual expression of CD8 and PD-L1 truly identifies an immune responsive subgroup of patients remains to be validated but represents a new starting point.”
References
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; Advance online publication 15 June 2021. https://doi.org/10.1016/S1470-2045(21)00216-3
Barber E, Matei D. Immunotherapy in ovarian cancer: we are not there yet. Lancet Oncol; Advance online publication 15 June 2021. https://doi.org/10.1016/S1470-2045(21)00303-X
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