Continuing a Cancer Treatment Despite Tumor Growth May Be Valuable: Sunitinib in Renal Cell Carcinoma as Example

PLoS One. 2014 May 5;9(5):e96316. doi: 10.1371/journal.pone.0096316. eCollection 2014.

Abstract

Background: The US FDA and the EMA have approved seven agents for the treatment of renal cell carcinoma, primarily based on differences in progression-free survival (PFS). Because PFS is an arbitrary endpoint we hypothesized that an analysis would demonstrate the growth rate of tumors remained constant at the time of RECIST-defined disease progression.

Methods: We previously estimated the growth (g) and regression (d) rates and the stability of g using data from the Phase III trial comparing sunitinib and interferon.

Results: Sufficient data were available and rate constants statistically valid in 321 of 374 patients randomized to sunitinib. Median d was 0•0052 days(-1); in 53 patients no tumor growth was recorded. Median g was 0•00082 days(-1) and was stable for a median of 275 days on therapy, remaining stable beyond 300, 600 and 900 days in 122, 65 and 27 patients, respectively. A possible increase in g while receiving sunitinib could be discerned in only 18 of 321 patients. Given a median g of 0•00082 days(-1) the estimated median time to a second progression were sunitinib continued past RECIST-defined progression was 7.3 months. At 100, 200, and 300 days after starting therapy, an estimated 47%, 27%, and 13% of tumor remains sunitinib sensitive and could explain a RECIST-defined response to a new TKI.

Conclusion: Prolonged stability of g with sunitinib suggests continued sunitinib beyond RECIST-defined progression may provide a beneficial outcome. Randomized trials in patients whose disease has "progressed" on sunitinib are needed to test this hypothesis.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Renal Cell / drug therapy*
  • Cell Proliferation / drug effects
  • Disease-Free Survival
  • Humans
  • Indoles / administration & dosage
  • Indoles / adverse effects
  • Indoles / therapeutic use*
  • Kidney Neoplasms
  • Pyrroles / administration & dosage
  • Pyrroles / adverse effects
  • Pyrroles / therapeutic use*
  • Sunitinib
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Indoles
  • Pyrroles
  • Sunitinib