Pivotal studies of axitinib and everolimus in 2nd-line mRC did not include pt treated with 1stPz. In addition, E vs A have not been directly compared in clinical trials in this setting. We aimed to compare the effectiveness of E vs A in real life, as second-line after pazopanib in mRC.
SPAZO2 (NCT03091465) was a retrospective real-world study to analyze the effectiveness of 1stPz and subsequent therapies in mRC in several settings in every day practice. Data from 530 pt treated with frontline pazopanib outside CT in 50 centers in Spain were collected by investigators, but monitored and entered in a database by an external CRO.
Out of 285 pt receiving 2nd-line targeted therapies after 1stPz, 189 received either Ax (88, 46.6%) or Ev (101, 53.4%). There were no significant differences (Ax vs Ev), in age (63 y vs 66 y), sex (68% vs 64% males), nephrectomy (76% vs 67%), metastases in lymph nodes (58% vs 52%), liver (21% vs 28%), bone (45% vs 41%), CNS (6%), adrenal (4% vs 5%), pleura/peritoneum (4% vs 6%), or pancreas (4% vs 6%), but there were in age >75 (14% vs 25%), nonclear cell component (1 vs 16%), and lung (85 vs 72%) and skin/soft-tissue (20 vs 28%) metastases. According to the IMDC for 2nd-line targeted therapies, 17% vs 9% of pt were in the favorable risk group, 65% vs 69% in the intermediate risk, and 18% vs 22% in the poor risk. All-grades hypertension (32.6% vs 3.6%) and hypothyroidism (16% vs 6%) were significantly higher with Ax, whereas anemia (21.4% vs 55%), and mucositis (12.3% vs 39%) were more frequent with Ev. Subsequent therapies were given in 56% in Ax vs 46% in Eve. After median follow-up of 28 mo, 74.6 of pt have died. Outcomes and 95%CI are summarized in the table.Table:
|ORR||SD||Median||6 monts||Median||1 year|
|Axitinib||13.1%||42.9%||5.3 (3-7)||47%||11.6 (7-16)||49%|
|Everolimus||9.3%||43%||4.6 (3-6)||39%||9.5 (7-12)||43%|
|Overall||11.2%||42.9%||5.0 (4-6)||43%||10.7 (8-13)||46%|
|p ns||HR*: 0.76 (0.5-1.1)||HR*: 0.81 (0.6-1.2)|
Adjusted by IMDC, metastases, age, histology and subsequent therapies.
In this real world study in pt with mRC, we could not find statistically significant differences in effectiveness between axitinib and everolimus as 2nd-line after 1st line pazopanib. These results validate the use of both drugs in terms of clinical benefit, PFS and OS.
Clinical trial identification
Legal entity responsible for the study
J. Arranz Arija: AdBo from Novartis and Pfizer. B. Pérez-Valderrama: Consulting/Advisory role for Astellas Pharma, Novartis, Pfizer, Pierre Fabre, Bayer, Sanofi, Bristol-Myers Squib and Roche. J. Puertas Alvarez: Participation in advisory board meetings from Pfizer, Astellas, Novartis, Sanofi, GlaxoSmithKline, AstraZeneca, Pharmamar, Hospira, Janssen, Eisai, Roche, Lilly, and Bayer. All other authors have declared no conflicts of interest.