In the Journals

Avelumab demonstrates antitumor activity in ovarian cancer

Avelumab demonstrated antitumor activity and safety among heavily pretreated patients with recurrent or refractory ovarian cancer, according to results from the JAVELIN solid tumor study published in JAMA Oncology.

Avelumab (Bavencio; EMD Serono, Pfizer) — approved for treatment of Merkel cell carcinoma and for locally advanced or metastatic urothelial carcinoma that progressed on platinum-containing chemotherapy — is a human immunoglobin GI monoclonal antibody that blocks PD-L1 in addition to activating adaptive immune responses by inhibiting interactions between PD-L1 and PD-1.

“Additional treatment options are needed to prolong OS and improve quality of life in patients with advanced ovarian cancer regardless of their treatment history,” Mary L. Disis, MD, Helen B. Slonaker endowed professorship for cancer research and professor in the department of medicine in the division of oncology, and director of tumor medicine at University of Washington School of Medicine, and colleagues wrote. “Increasing evidence indicates that immune responses may influence patient outcomes in ovarian cancer. ... Ovarian tumor cells often express the immune checkpoint protein PD-L1 and tumor-infiltrating lymphocytes often express its receptor (PD-1). The interaction between PD-1 and PD-L1 is a key therapeutic target for reactivating immune responses against multiple cancers; thus, agents targeting this interaction could provide therapeutic benefit in ovarian cancer.”

In the expansion cohort of a phase 1b-open label study, Disis and colleagues evaluated 125 women (median age, 62 years; range, 27-84; median previous lines of treatment, 3; range, 0-10) with advanced ovarian cancer who previously underwent platinum-based chemotherapy.

Median follow-up was 26.6 months (range, 16-38 months), and median duration of avelumab treatment was 2.8 months (range, 0.5-27.4).

The researchers found that 12 patients (ORR, 9.6%; 95% CI, 5.1-16.2) achieved a confirmed objective response, with one patient (0.8%) achieving a complete response and 11 patients (8.8%) achieving partial response.

Median PFS was 2.6 months (95% CI, 1.4-2.8). The rate of 6-month PFS was 16.1% (95% CI, 10.1-23.4) and the rate of 1-year PFS was 10.2% (95% CI, 5.4-16.7).

Median OS was 11.2 months (95% CI, 8.7-15.4).

Most of the patients (97.6%; n = 122) experienced an adverse event. This included 86 patients (68.8%) who had a treatment-associated adverse event. Twenty-five patients (20%) experienced infusion-related reactions.

Other common treatment-related adverse events included fatigue (13.6%; n = 17), diarrhea (12%; n = 15) and nausea (11.2%; n = 14).

Nine patients (7.2%) experienced grade 3 or higher treatment-related adverse events, and only increased levels of lipase (2.4%; n = 3) was seen in more than one patent.

Immune-related adverse events of any grade occurred in 16.8% (n = 21) of patients. There were no treatment-related deaths.

The researchers noted the early-phase, single-arm design and the limited number of responding patients as study limitations.

“Although response and survival findings with avelumab monotherapy in this study are encouraging, it would be of interest to determine whether efficacy can be increased though combination or sequential regimens involving chemotherapy or PARP inhibitors,” the researchers wrote. “Two global phase 3 trials of avelumab in combination with chemotherapy have been initiated in patients with ovarian cancer.”

One of those trials, JAVELIN Ovarian 100, a three-arm trial comparing first-line carboplatin and paclitaxel chemotherapy alone or with avelumab, was terminated after it failed to achieve its primary endpoint of PFS. The finding was reported this month as part of a planned interim analysis. – by Jennifer Byrne

Disclosures: Disis reports research funding from Celgene, EMD Serono, Epiphany, Janssen, Pfizer and Seattle Genetics; stock in Epiphany; and being an inventor on patents held by University of Washington. Please see the study for all other authors’ relevant financial disclosures.

Avelumab demonstrated antitumor activity and safety among heavily pretreated patients with recurrent or refractory ovarian cancer, according to results from the JAVELIN solid tumor study published in JAMA Oncology.

Avelumab (Bavencio; EMD Serono, Pfizer) — approved for treatment of Merkel cell carcinoma and for locally advanced or metastatic urothelial carcinoma that progressed on platinum-containing chemotherapy — is a human immunoglobin GI monoclonal antibody that blocks PD-L1 in addition to activating adaptive immune responses by inhibiting interactions between PD-L1 and PD-1.

“Additional treatment options are needed to prolong OS and improve quality of life in patients with advanced ovarian cancer regardless of their treatment history,” Mary L. Disis, MD, Helen B. Slonaker endowed professorship for cancer research and professor in the department of medicine in the division of oncology, and director of tumor medicine at University of Washington School of Medicine, and colleagues wrote. “Increasing evidence indicates that immune responses may influence patient outcomes in ovarian cancer. ... Ovarian tumor cells often express the immune checkpoint protein PD-L1 and tumor-infiltrating lymphocytes often express its receptor (PD-1). The interaction between PD-1 and PD-L1 is a key therapeutic target for reactivating immune responses against multiple cancers; thus, agents targeting this interaction could provide therapeutic benefit in ovarian cancer.”

In the expansion cohort of a phase 1b-open label study, Disis and colleagues evaluated 125 women (median age, 62 years; range, 27-84; median previous lines of treatment, 3; range, 0-10) with advanced ovarian cancer who previously underwent platinum-based chemotherapy.

Median follow-up was 26.6 months (range, 16-38 months), and median duration of avelumab treatment was 2.8 months (range, 0.5-27.4).

The researchers found that 12 patients (ORR, 9.6%; 95% CI, 5.1-16.2) achieved a confirmed objective response, with one patient (0.8%) achieving a complete response and 11 patients (8.8%) achieving partial response.

Median PFS was 2.6 months (95% CI, 1.4-2.8). The rate of 6-month PFS was 16.1% (95% CI, 10.1-23.4) and the rate of 1-year PFS was 10.2% (95% CI, 5.4-16.7).

Median OS was 11.2 months (95% CI, 8.7-15.4).

Most of the patients (97.6%; n = 122) experienced an adverse event. This included 86 patients (68.8%) who had a treatment-associated adverse event. Twenty-five patients (20%) experienced infusion-related reactions.

Other common treatment-related adverse events included fatigue (13.6%; n = 17), diarrhea (12%; n = 15) and nausea (11.2%; n = 14).

Nine patients (7.2%) experienced grade 3 or higher treatment-related adverse events, and only increased levels of lipase (2.4%; n = 3) was seen in more than one patent.

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Immune-related adverse events of any grade occurred in 16.8% (n = 21) of patients. There were no treatment-related deaths.

The researchers noted the early-phase, single-arm design and the limited number of responding patients as study limitations.

“Although response and survival findings with avelumab monotherapy in this study are encouraging, it would be of interest to determine whether efficacy can be increased though combination or sequential regimens involving chemotherapy or PARP inhibitors,” the researchers wrote. “Two global phase 3 trials of avelumab in combination with chemotherapy have been initiated in patients with ovarian cancer.”

One of those trials, JAVELIN Ovarian 100, a three-arm trial comparing first-line carboplatin and paclitaxel chemotherapy alone or with avelumab, was terminated after it failed to achieve its primary endpoint of PFS. The finding was reported this month as part of a planned interim analysis. – by Jennifer Byrne

Disclosures: Disis reports research funding from Celgene, EMD Serono, Epiphany, Janssen, Pfizer and Seattle Genetics; stock in Epiphany; and being an inventor on patents held by University of Washington. Please see the study for all other authors’ relevant financial disclosures.

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