Platinum-resistant / refractory ovarian cancer: Avelumab alone or in combination with pegylated liposomal Doxorubicin did not meet the primary endpoints of overall survival or progression-free survival
The phase III JAVELIN Ovarian 200 trial evaluating Avelumab ( Bavencio ) alone or in combination with pegylated liposomal Doxorubicin ( PLD ), a type of chemotherapy, compared with PLD did not meet the prespecified primary endpoints of overall survival ( OS ) or progression-free survival ( PFS ) in patients with Platinum-resistant or -refractory ovarian cancer.
Signals were observed in the combination arm relative to PLD, and further analyses of the trial are warranted ( hazard ratio, HR for the primary PFS endpoint for Avelumab + PLD versus PLD alone: 0.78 [ repeated confidence interval ( RCI ): 0.587, 1.244; one-sided p-value: 0.0301 ]; HR for the primary OS endpoint for Avelumab + PLD vs PLD alone: 0.89 [ RCI: 0.744, 1.241; one-sided p-value: 0.2082 ]; HR for the primary PFS endpoint for Avelumab alone vs PLD alone: 1.68 [ RCI: 1.320, 2.601; one-sided p-value: more than 0.99 ]; HR for the primary OS endpoint for Avelumab alone vs PLD alone: 1.14 [ RCI: 0.948, 1.580; one-sided p-value: 0.8253 ]; objective response, a secondary endpoint: 13.3% [ 95% CI 8.8, 19.0 ] for Avelumab + PLD; 3.7% [ 95% CI 1.5, 7.5 ] for Avelumab alone; and 4.2% [ 95% CI 1.8, 8.1 ] for PLD alone ).
No new safety signals were observed for Avelumab alone or in combination, and the safety profile for Avelumab in this trial was consistent with that observed in the overall JAVELIN clinical development program.
JAVELIN Ovarian 200 enrolled a high proportion of patients with aggressive, refractory disease that had no response to prior Platinum-based chemotherapy, a population known to have disease that is challenging to treat; as such, this group of patients is typically not included in phase III ovarian cancer trials.
Although overall survival and progression-free survival did not reach statistical significance, study results indicate potential clinical activity of the combination of Avelumab and chemotherapy.
Four out of five patients with ovarian cancer are diagnosed at advanced stages. The disease often has no symptoms early on, when it is much more treatable.
Approximately 70% of patients with ovarian cancer who receive standard-of-care, frontline, Platinum-based chemotherapy will relapse in the first three years.
At first relapse, approximately 20% to 25% of ovarian cancer patients have Platinum-resistant or -refractory disease, and eventually almost all patients will become Platinum-resistant.
Avelumab is a human anti-programmed death ligand-1 ( PD-L1 ) antibody.
Avelumab has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, Avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.
Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity ( ADCC ) in vitro. ( Xagena )
Source: Pfizer, 2018