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HONOLULU – Combining avelumab with pegylated liposomal doxorubicin (PLD) may provide a survival benefit in certain patients with platinum-resistant or refractory epithelial ovarian cancer, a phase 3 trial suggests.
In the overall study population, progression-free survival (PFS) and overall survival (OS) rates were not significantly different for patients who received avelumab plus PLD and those who received avelumab or PLD alone.
However, some subgroups did experience survival benefits with the combination, including patients who were positive for programmed death–ligand 1 (PD-L1) and those who had received two or three prior lines of therapy.
Eric Pujade-Lauraine, MD, PhD, of ARCAGY-GINECO in Paris, presented these results from the JAVELIN Ovarian 200 trial at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
The trial enrolled 566 patients with platinum-resistant or refractory epithelial ovarian cancer. They were not preselected for PD-L1 expression.
Patients were randomized 1:1:1 to receive avelumab at 10 mg/kg every 2 weeks (n = 188), avelumab plus PLD at 40 mg/m2 every 4 weeks (n = 188), or PLD (n = 190).
Baseline characteristics were similar across the treatment arms. The median age was 61 in the avelumab arm and 60 in the other two arms (range, 26-86 years). In each arm, about 37% of patients had bulky disease, and all but two patients (both in the avelumab arm) had an Eastern Cooperative Oncology Group performance status of 0 or 1.
Nearly half of patients had received one line of prior therapy, and the rest had received two or three prior lines of therapy. About 75% of patients had platinum-resistant disease, and 25% were platinum refractory.
The median duration of study treatment was 10.1 weeks in the avelumab arm and 16.0 weeks in the pegylated liposomal doxorubicin (PLD) arm. In the combination arm, the median treatment duration was 16.9 weeks for avelumab and 16.3 weeks for PLD. In each arm, the most common reason for treatment discontinuation was disease progression.
Safety
Dr. Pujade-Lauraine said no new safety signals were observed with avelumab alone or in combination.
Serious treatment-related adverse events (AEs) occurred in 7.5% of patients in the avelumab arm, 17.6% of patients in the combination arm, and 10.7% of patients in the PLD arm. Discontinuation because of a treatment-related AE occurred in 6.4%, 4.4%, and 7.3% of patients, respectively.
There was one treatment-related AE leading to death in the avelumab arm and one in the PLD arm.
AEs that were more common in the combination arm than in the avelumab and PLD arms (respectively) were fatigue/asthenia (42.3%, 26.7%, and 28.8%), rash (34.1%, 8.0%, and 16.9%), stomatitis (28.0%, 2.1%, and 20.3%), and palmar-plantar erythrodysesthesia syndrome (33.0%, 0.5%, and 22.6%).
Response
The objective response rate was 3.7% in the avelumab arm, 13.3% in the combination arm, and 4.2% in the PLD arm. There were two complete responses; both occurred in the combination arm.
The response rate was significantly higher in the combination arm (odds ratio, 3.458, P = .0018) than in the PLD arm, but there was no significant difference in response rate between the avelumab arm and the PLD arm (OR, 0.890, P = .8280).
The median duration of response was 9.2 months in the avelumab arm, 8.5 months in the combination arm, and 13.1 months in the PLD arm.
Survival
There was a trend toward improved PFS with avelumab plus PLD, but the significance threshold was not met.
The median PFS was 1.9 months in the avelumab arm, 3.7 months in the combination arm, and 3.5 months in the PLD arm. With the PLD arm as a reference, the stratified hazard ratio was 1.68 for the avelumab arm (P greater than .999) and 0.78 for the combination arm (P = .0301).
The median OS was 11.8 months in the avelumab arm, 15.7 months in the combination arm, and 13.1 months in the PLD arm. The HR was 1.14 for the avelumab arm (P = .8253) and 0.89 for the combination arm (P = .2082).
“[A]velumab plus PLD showed clinical activity, but, in this unselected population, the trial did not meet the primary objective [of improving PFS or OS compared to PLD alone],” Dr. Pujade-Lauraine noted. “However, prespecified analyses indicate a potential role of PD-L1 expression as a predictor of clinical benefit.”
When Dr. Pujade-Lauraine and his colleagues looked at patients who were positive for PD-L1 (57%), the researchers found a significant improvement in PFS, but not OS, with avelumab plus PLD.
The median PFS was 1.9 months in the avelumab arm (HR,1.45, P = .0303), 3.7 months in the combination arm (HR, 0.65, P = .0143), and 3.0 months in the PLD arm.
The median OS was 13.7 months in the avelumab arm (HR, 0.83, P = .3580), 17.7 months in the combination arm (HR, 0.72, P = .0842), and 13.1 months in the PLD arm.
The researchers also found that PFS and OS were better with avelumab plus PLD versus PLD alone among patients who had received two or three prior treatment regimens at baseline. The HR was 0.62 for PFS and 0.64 for OS.
Dr. Pujade-Lauraine said further subgroup analyses are ongoing.
This trial was sponsored by Pfizer. Dr. Pujade-Lauraine reported relationships with AstraZeneca, Clovis Oncology, Incyte, Pfizer, Roche, and Tesaro.
SOURCE: Pujade-Lauraine E et al. SGO 2019, Abstract LBA1.
HONOLULU – Combining avelumab with pegylated liposomal doxorubicin (PLD) may provide a survival benefit in certain patients with platinum-resistant or refractory epithelial ovarian cancer, a phase 3 trial suggests.
In the overall study population, progression-free survival (PFS) and overall survival (OS) rates were not significantly different for patients who received avelumab plus PLD and those who received avelumab or PLD alone.
However, some subgroups did experience survival benefits with the combination, including patients who were positive for programmed death–ligand 1 (PD-L1) and those who had received two or three prior lines of therapy.
Eric Pujade-Lauraine, MD, PhD, of ARCAGY-GINECO in Paris, presented these results from the JAVELIN Ovarian 200 trial at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
The trial enrolled 566 patients with platinum-resistant or refractory epithelial ovarian cancer. They were not preselected for PD-L1 expression.
Patients were randomized 1:1:1 to receive avelumab at 10 mg/kg every 2 weeks (n = 188), avelumab plus PLD at 40 mg/m2 every 4 weeks (n = 188), or PLD (n = 190).
Baseline characteristics were similar across the treatment arms. The median age was 61 in the avelumab arm and 60 in the other two arms (range, 26-86 years). In each arm, about 37% of patients had bulky disease, and all but two patients (both in the avelumab arm) had an Eastern Cooperative Oncology Group performance status of 0 or 1.
Nearly half of patients had received one line of prior therapy, and the rest had received two or three prior lines of therapy. About 75% of patients had platinum-resistant disease, and 25% were platinum refractory.
The median duration of study treatment was 10.1 weeks in the avelumab arm and 16.0 weeks in the pegylated liposomal doxorubicin (PLD) arm. In the combination arm, the median treatment duration was 16.9 weeks for avelumab and 16.3 weeks for PLD. In each arm, the most common reason for treatment discontinuation was disease progression.
Safety
Dr. Pujade-Lauraine said no new safety signals were observed with avelumab alone or in combination.
Serious treatment-related adverse events (AEs) occurred in 7.5% of patients in the avelumab arm, 17.6% of patients in the combination arm, and 10.7% of patients in the PLD arm. Discontinuation because of a treatment-related AE occurred in 6.4%, 4.4%, and 7.3% of patients, respectively.
There was one treatment-related AE leading to death in the avelumab arm and one in the PLD arm.
AEs that were more common in the combination arm than in the avelumab and PLD arms (respectively) were fatigue/asthenia (42.3%, 26.7%, and 28.8%), rash (34.1%, 8.0%, and 16.9%), stomatitis (28.0%, 2.1%, and 20.3%), and palmar-plantar erythrodysesthesia syndrome (33.0%, 0.5%, and 22.6%).
Response
The objective response rate was 3.7% in the avelumab arm, 13.3% in the combination arm, and 4.2% in the PLD arm. There were two complete responses; both occurred in the combination arm.
The response rate was significantly higher in the combination arm (odds ratio, 3.458, P = .0018) than in the PLD arm, but there was no significant difference in response rate between the avelumab arm and the PLD arm (OR, 0.890, P = .8280).
The median duration of response was 9.2 months in the avelumab arm, 8.5 months in the combination arm, and 13.1 months in the PLD arm.
Survival
There was a trend toward improved PFS with avelumab plus PLD, but the significance threshold was not met.
The median PFS was 1.9 months in the avelumab arm, 3.7 months in the combination arm, and 3.5 months in the PLD arm. With the PLD arm as a reference, the stratified hazard ratio was 1.68 for the avelumab arm (P greater than .999) and 0.78 for the combination arm (P = .0301).
The median OS was 11.8 months in the avelumab arm, 15.7 months in the combination arm, and 13.1 months in the PLD arm. The HR was 1.14 for the avelumab arm (P = .8253) and 0.89 for the combination arm (P = .2082).
“[A]velumab plus PLD showed clinical activity, but, in this unselected population, the trial did not meet the primary objective [of improving PFS or OS compared to PLD alone],” Dr. Pujade-Lauraine noted. “However, prespecified analyses indicate a potential role of PD-L1 expression as a predictor of clinical benefit.”
When Dr. Pujade-Lauraine and his colleagues looked at patients who were positive for PD-L1 (57%), the researchers found a significant improvement in PFS, but not OS, with avelumab plus PLD.
The median PFS was 1.9 months in the avelumab arm (HR,1.45, P = .0303), 3.7 months in the combination arm (HR, 0.65, P = .0143), and 3.0 months in the PLD arm.
The median OS was 13.7 months in the avelumab arm (HR, 0.83, P = .3580), 17.7 months in the combination arm (HR, 0.72, P = .0842), and 13.1 months in the PLD arm.
The researchers also found that PFS and OS were better with avelumab plus PLD versus PLD alone among patients who had received two or three prior treatment regimens at baseline. The HR was 0.62 for PFS and 0.64 for OS.
Dr. Pujade-Lauraine said further subgroup analyses are ongoing.
This trial was sponsored by Pfizer. Dr. Pujade-Lauraine reported relationships with AstraZeneca, Clovis Oncology, Incyte, Pfizer, Roche, and Tesaro.
SOURCE: Pujade-Lauraine E et al. SGO 2019, Abstract LBA1.
HONOLULU – Combining avelumab with pegylated liposomal doxorubicin (PLD) may provide a survival benefit in certain patients with platinum-resistant or refractory epithelial ovarian cancer, a phase 3 trial suggests.
In the overall study population, progression-free survival (PFS) and overall survival (OS) rates were not significantly different for patients who received avelumab plus PLD and those who received avelumab or PLD alone.
However, some subgroups did experience survival benefits with the combination, including patients who were positive for programmed death–ligand 1 (PD-L1) and those who had received two or three prior lines of therapy.
Eric Pujade-Lauraine, MD, PhD, of ARCAGY-GINECO in Paris, presented these results from the JAVELIN Ovarian 200 trial at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
The trial enrolled 566 patients with platinum-resistant or refractory epithelial ovarian cancer. They were not preselected for PD-L1 expression.
Patients were randomized 1:1:1 to receive avelumab at 10 mg/kg every 2 weeks (n = 188), avelumab plus PLD at 40 mg/m2 every 4 weeks (n = 188), or PLD (n = 190).
Baseline characteristics were similar across the treatment arms. The median age was 61 in the avelumab arm and 60 in the other two arms (range, 26-86 years). In each arm, about 37% of patients had bulky disease, and all but two patients (both in the avelumab arm) had an Eastern Cooperative Oncology Group performance status of 0 or 1.
Nearly half of patients had received one line of prior therapy, and the rest had received two or three prior lines of therapy. About 75% of patients had platinum-resistant disease, and 25% were platinum refractory.
The median duration of study treatment was 10.1 weeks in the avelumab arm and 16.0 weeks in the pegylated liposomal doxorubicin (PLD) arm. In the combination arm, the median treatment duration was 16.9 weeks for avelumab and 16.3 weeks for PLD. In each arm, the most common reason for treatment discontinuation was disease progression.
Safety
Dr. Pujade-Lauraine said no new safety signals were observed with avelumab alone or in combination.
Serious treatment-related adverse events (AEs) occurred in 7.5% of patients in the avelumab arm, 17.6% of patients in the combination arm, and 10.7% of patients in the PLD arm. Discontinuation because of a treatment-related AE occurred in 6.4%, 4.4%, and 7.3% of patients, respectively.
There was one treatment-related AE leading to death in the avelumab arm and one in the PLD arm.
AEs that were more common in the combination arm than in the avelumab and PLD arms (respectively) were fatigue/asthenia (42.3%, 26.7%, and 28.8%), rash (34.1%, 8.0%, and 16.9%), stomatitis (28.0%, 2.1%, and 20.3%), and palmar-plantar erythrodysesthesia syndrome (33.0%, 0.5%, and 22.6%).
Response
The objective response rate was 3.7% in the avelumab arm, 13.3% in the combination arm, and 4.2% in the PLD arm. There were two complete responses; both occurred in the combination arm.
The response rate was significantly higher in the combination arm (odds ratio, 3.458, P = .0018) than in the PLD arm, but there was no significant difference in response rate between the avelumab arm and the PLD arm (OR, 0.890, P = .8280).
The median duration of response was 9.2 months in the avelumab arm, 8.5 months in the combination arm, and 13.1 months in the PLD arm.
Survival
There was a trend toward improved PFS with avelumab plus PLD, but the significance threshold was not met.
The median PFS was 1.9 months in the avelumab arm, 3.7 months in the combination arm, and 3.5 months in the PLD arm. With the PLD arm as a reference, the stratified hazard ratio was 1.68 for the avelumab arm (P greater than .999) and 0.78 for the combination arm (P = .0301).
The median OS was 11.8 months in the avelumab arm, 15.7 months in the combination arm, and 13.1 months in the PLD arm. The HR was 1.14 for the avelumab arm (P = .8253) and 0.89 for the combination arm (P = .2082).
“[A]velumab plus PLD showed clinical activity, but, in this unselected population, the trial did not meet the primary objective [of improving PFS or OS compared to PLD alone],” Dr. Pujade-Lauraine noted. “However, prespecified analyses indicate a potential role of PD-L1 expression as a predictor of clinical benefit.”
When Dr. Pujade-Lauraine and his colleagues looked at patients who were positive for PD-L1 (57%), the researchers found a significant improvement in PFS, but not OS, with avelumab plus PLD.
The median PFS was 1.9 months in the avelumab arm (HR,1.45, P = .0303), 3.7 months in the combination arm (HR, 0.65, P = .0143), and 3.0 months in the PLD arm.
The median OS was 13.7 months in the avelumab arm (HR, 0.83, P = .3580), 17.7 months in the combination arm (HR, 0.72, P = .0842), and 13.1 months in the PLD arm.
The researchers also found that PFS and OS were better with avelumab plus PLD versus PLD alone among patients who had received two or three prior treatment regimens at baseline. The HR was 0.62 for PFS and 0.64 for OS.
Dr. Pujade-Lauraine said further subgroup analyses are ongoing.
This trial was sponsored by Pfizer. Dr. Pujade-Lauraine reported relationships with AstraZeneca, Clovis Oncology, Incyte, Pfizer, Roche, and Tesaro.
SOURCE: Pujade-Lauraine E et al. SGO 2019, Abstract LBA1.
REPORTING FROM SGO 2019