The US Food and Drug Administration ( FDA ) has approved Bavencio ( Avelumab ) in combination with Inlyta ( Axitinib ) for the first-line treatment of patients with advanced renal cell carcinoma ( RCC ).
This is the first FDA approval for an anti-PD-L1 therapy as part of a combination regimen for patients with advanced renal cell carcinoma.
The approval of Bavencio in combination with Inlyta was based on positive results from the phase III JAVELIN Renal 101 study, in which the combination significantly improved median progression-free survival ( PFS ) compared with Sunitinib ( Sutent ) by more than five months in the intent-to-treat ( ITT ) patient population ( hazard ratio, HR=0.69 [ 95% CI: 0.56–0.84 ]; 2-sided p-value=0.0002; median PFS for Avelumab in combination with Axitinib: 13.8 months [ 95% CI: 11.1-NE ]; Sunitinib: 8.4 months [ 95% CI: 6.9-11.1 ] ).
The ITT population included patients regardless of PD-L1 expression and across IMDC ( International Metastatic Renal Cell Carcinoma Database ) prognostic risk groups ( favorable 21%, intermediate 62% and poor 16% ).
In JAVELIN Renal 101, the objective response rate ( ORR ) was doubled in the ITT population with Avelumab in combination with Axitinib versus Sunitinib ( 51.4% [ 95% CI: 46.6-56.1 ] versus 25.7% [ 95% CI: 21.7-30.0 ] ).
With a median overall survival ( OS ) follow-up of 19 months, data for the trial’s other primary endpoint of OS were immature, with 27% of deaths in the ITT population, and the trial is continuing as planned.
The most common adverse reactions ( greater than or equal to 20% ) were diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain and headache.
Serious adverse reactions occurred in 35% of patients receiving Avelumab in combination with Axitinib.
The incidence of major adverse cardiovascular events ( MACE ) was higher with Avelumab in combination with Axitinib versus Sunitinib.
In 2019, an estimated 73,820 new cases of kidney cancer will be diagnosed in the US, and approximately 14,770 people will die from the disease.
RCC is the most common form of kidney cancer, accounting for about 2% to 3% of all cancers in adults.
Approximately 20% to 30% of patients with kidney cancer are first diagnosed at the advanced stage.
The five-year survival rate for patients with metastatic RCC is approximately 12%.
JAVELIN Renal 101 trial is a randomized ( 1:1 ), multicenter, open-label study of Avelumab in combination with Axitinib in 886 patients with untreated advanced RCC regardless of tumor PD-L1 expression [ intent-to-treat ( ITT ) population ].
Patients with autoimmune disease or conditions requiring systemic immunosuppression were excluded.
The major efficacy outcome measures were PFS as assessed by BICR ( Blinded Independent Central Review ) using RECIST v1.1 and OS in patients with PD-L1-positive tumors using a clinical trial assay ( PD-L1 expression level greater than or equal to 1% ).
If PFS was statistically significant in patients with PD-L1-positive tumors, it was then tested in the ITT population.
The hazard ratio for PFS in patients with PD-L1-positive tumors was hazard ratio 0.61 ( 95% CI: 0.48, 0.79 ). PFS and OS in the ITT population, overall response and safety are included as secondary endpoints. ( Xagena )
Source: Pfizer, 2019