Patients with recurrent ovarian cancer (ROC) did not experience better outcomes when receiving maintenance therapy with immunotherapy Tecentriq (atezolizumab) plus PARP inhibitor Zejula (niraparib) and chemotherapy, according to findings from a phase 3 trial presented at the 2023 ESMO Congress.
Eligible patients were randomly assigned 1:1 to receive either Tecentriq or placebo plus chemotherapy for six cycles. After this, patients received Tecentriq or placebo on day 1 plus Zejula at an individualized starting dose on days 1 through 21 every 21 days as maintenance therapy until disease progression.
In the phase 3 ANITA trial, the primary endpoint, or the main result measured at the end of study to see if treatment worked, was investigator-assessed progression-free survival (PFS; length of time from the start of treatment until after when the disease does not worsen).
Secondary end points included objective response rate (ORR; percentage of patients in the study who had a partial or complete response to treatment), overall survival (OS; length of time from diagnosis or start of treatment when a patient remains alive), PFS from the start of maintenance, safety and patient-reported outcomes.
The baseline patient characteristics were generally well balanced between the Tecentriq and placebo arms; the median age was 63 years compared with 62 years, respectively. Most patients in both arms had had undergone one prior line of therapy and had a platinum therapy-free interval of over 12 months. A majority of patients in both arms also had negative PD-L1 status (56% vs. 54%) and did not have BRCA-mutated disease (87% vs. 85%).
At a median follow-up of 36 months, 208 patients who received the PD-L1 inhibitor in addition to chemotherapy with a Paraplatin (carboplatin)-containing doublet and maintenance experienced a median PFS of 11.2 months. Among the 209 patients who were treated with placebo in place of Tecentriq, there was a median PFS of 10.1 months.
No significant PFS benefit was observed with the addition of Tecentriq among patients with PD-L1-positive disease, PD-L1-negative disease or those with PD-L1 non-informative status.
The researchers reported that the study missed its primary end point of investigator-assessed PFS.
“Despite strong preclinical rationale, previous phase 3 trials have shown no benefit from the addition of a PD-L1 inhibitor to chemotherapy plus or minus (Avastin)for patients with newly diagnosed or recurrent ovarian cancer,” Dr. Antonio Gonzalez-Martin, director of the department of medical oncology, a specialist in medical oncology and the director of the Cancer Center Clínica Universidad de Navarra in Madrid, Spain and president of the Spanish Ovarian Cancer Group, said during the presentation.
“The (phase 3) DUO-O trial showed an improved PFS with the addition of (Imfinzi) plus (Lynparza) to frontline chemotherapy plus Avastin in patients with non-tBRCA-mutated advanced ovarian cancer,” Gonzalez-Martin said. “(However), the contribution of a PARP inhibitor plus a checkpoint inhibitor with or without Avastin remains unknown. ANITA is the first reported phase 3 study evaluating an immune checkpoint inhibitor with platinum chemotherapy plus PARP inhibitor maintenance in late-relapsing ROC.”
ANITA was a multicenter study that enrolled patients with high-grade serous, endometrioid, or undifferentiated ROC. To be included in the study, patients needed to be immune checkpoint inhibitor naïve and have a platinum therapy-free interval of more than six months.
Patients were permitted to receive up to two prior lines of chemotherapy and a mandatory de novo biopsy was also required. Prior treatment with a PARP inhibitor for ROC was not allowed.
Additional data demonstrated that patients in the Tecentriq arm experienced an ORR of 45% during chemotherapy compared with 43% in the placebo arm. Some patients in both arms experienced complete responses (7% vs. 6% respectively) and stable disease (44% vs. 46%).
Fifty-seven patients in the Tecentriq arm did not start maintenance therapy, due to PD (42 patients), death (three patients), toxicity (four patients), withdrawal (four patients) and other reasons (four patients.
In the placebo arm, 53 patients did not start maintenance due to PD (37 patients), death (five patients), toxicity (three patients), withdrawal (four patients) and other reasons (four patients).
The median PFS from the start of maintenance was 6.7 months for 150 patients in the Tecentriq arm, compared with 5.3 months for 156 patients in the placebo arm.
In the PFS subgroup analysis, the only patients who experienced a significant PFS benefit with the addition of Tecentriq were those with non-mutated BRCA status and those whose chemotherapy backbone contained Gemzar (gemcitabine).
All other subgroups either experienced a non-statistically significant benefit with Tecentriq or displayed PFS findings that favored the placebo arm.
In terms of safety, any-grade side effects occurred in 97% of patients in both the Tecentriq and placebo arms. Patients in both arms experienced grade 3 or higher treatment-related side effects, serious side effects, immune-mediated side effects and side effects leading to Zejula dose reduction.
Two patients in the Tecentriq arm died due to treatment-related side effects.
The most common non-hematological any-grade side effects observed during the chemotherapy phase in both the Tecentriq and placebo arms were asthenia (weakness), nausea and constipation; these were also the most common in both arms during the maintenance phase.
During the chemotherapy phase, approximately 60% of patients experienced anemia and neutropenia (lower levels of white blood cells) in the placebo arm compared with approximately 45% and 55%, respectively, in the Tecentriq arm.
“The safety profile was predictable and manageable and no new safety signals with Tecentriq in combination with chemotherapy and maintenance Zejula were observed,” Gonzalez-Martin said. “Survival follow-up as well as other secondary endpoints and biomarker research is still ongoing. We can conclude that ANITA provides relevant information for the interpretation of other phase 3 trials with checkpoint inhibitors and PARP inhibitors in ovarian cancer.”
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