Exposure to Multiple Lines of Treatment and Survival of Patients With Metastatic Renal Cell Carcinoma: A Real-world Analysis - Beyond the Abstract

In the past decade, the introduction of new therapeutic agents has improved the survival of patients with metastatic RCC (mRCC). The 5-year survival for RCC has improved from 52% in 1975 to 74% in 2014. 

Recently, a better understanding of the biologic and molecular basis of kidney cancer has led to the development and approval of new targeted agents. Many of these are directed against the vascular endothelial growth factor receptors (e.g., bevacizumab, sorafenib, sunitinib, pazopanib, axitinib, cabozantinib), the mammalian target of rapamycin pathway (e.g., everolimus and temsirolimus), and the programmed cell death1/programmed cell death ligand 1 pathway (e.g., nivolumab). With the advent of targeted agents, improvements in clinical outcomes occurred, with response rates > 30% and median overall survival (mOS) of almost 2 years, depending on the patient risk profile, agent used, and other clinical variables1.

Considering the evolution of the standard of care in the treatment of mRCC, we sought to determine whether these changes had directly translated into a survival benefit in clinical practice. Our aim was to clarify whether improvements in mRCC survival were also present in a “real-world” cohort of patients. We retrospectively collected data from 500 mRCC patients treated at Istituto Nazionale dei Tumori (Milan, Italy). Thus, we examined the difference in exposure to multiple lines of treatment and OS between patients who started therapy for mRCC in 2 different periods (period 1, 2004-2010; and period 2, 2011-2017). We reviewed our real-world clinical practice for mRCC and investigated the difference in OS and trends in exposure to multiple lines of treatment between patients who had started first-line therapy in the 2 periods.

In our analysis, a significant improvement in OS occurred during the more recent treatment period in the mRCC population, from a mOS of 22.8 months for 2004 to 2010 to 38.2 months for 2011 to 2017 (Figure 1). However, the difference did not reach statistical significance on multivariate analysis. We also found an increase in period 2 in the number of patients who received more therapeutic lines at PD compared with patients treated in period 1.

This improvement over the years can be explained by the intensified medical and surgical strategies used in a multidisciplinary approach, with the aim of providing optimal treatment to patients during the course of the disease2.  Second, for patients who started treatment between 2011 and 2017, 4 new therapeutic agents for the treatment of mRCC were available in Italy (e.g., axitinib, pazopanib, nivolumab, cabozantinib). The availability of new drugs has increased the lines of treatment received by patients. Thus, the survival of patients receiving more therapeutic agents has increased. A significant association between increased survival and treatment after first-line therapy has been highlighted3. In our analysis, we found that patients treated in period 2 were more likely to receive different therapeutic lines at PD compared with those treated in period 1.

Third, in view of an increased number of drugs available, therapy and adverse event management has also improved. The new schedules have allowed one to tailor treatment to the patient characteristics4, allowing patients to be treated for as long as possible.

These real-life data support and confirm the positive effect of novel therapies and a multimodal approach for mRCC. The prognosis of mRCC patients will likely continue to improve with optimization of the current targeted therapy and approval of novel agents with different mechanisms of action.

Figure 1 - Kaplan-Meier Estimates of Overall Survival (OS) for Patients Treated in Period 1 and Period 2.
Kaplan Meier Estimates of Overall Survival

Written by: Raffaele Ratta, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

References:

  1. Albiges, T. Choueiri, B. Escudier, et al. A systematic review of sequencing and combinations of systemic therapy in metastatic renal cancer. Eur Urol, 67 (2014), pp. 100-110.
  2. Mennitto, E. Verzoni, G. Calareso, et al. Treatment of advanced renal cell carcinoma: recent advances and current role of immunotherapy, surgery, and cryotherapy. Tumori, 103 (2017), pp. 15-21.
  3. Wagstaff, R. Jones, R. Hawkins, et al. Treatment patterns and clinical outcomes in patients with renal cell carcinoma in the UK: insights from the RECCORD registry. Ann Oncol, 27 (2016), pp. 159-165.
  4. Bracarda, R. Iacovelli, L. Boni, et al. Sunitinib administered on 2/1 schedule in patients with metastatic renal cell carcinoma: the RAINBOW analysis. Ann Oncol, 26 (2015), pp. 2107-2113.

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