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

<div><p>Background</p><p>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.</p><p>Methods</p><p>We previously estimated the growth (<b>g</b>) and regression (<b>d</b>) rates and the stability of <b>g</b> using data from the Phase III trial comparing sunitinib and interferon.</p><p>Results</p><p>Sufficient data were available and rate constants statistically valid in 321 of 374 patients randomized to sunitinib. Median <b>d</b> was 0•0052 days⁻¹; in 53 patients no tumor growth was recorded. Median <b>g</b> 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 <b>g</b> while receiving sunitinib could be discerned in only 18 of 321 patients. Given a median <b>g</b> 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.</p><p>Conclusion</p><p>Prolonged stability of <b>g</b> 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.</p>