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Immediate chemotherapy after radical cystectomy failed to extend OS
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Patients with urothelial carcinoma of the bladder who underwent immediate chemotherapy after radical cystectomy or bilateral lymphadenectomy demonstrated comparable OS to those who underwent delayed chemotherapy, according to phase 3 study results.
Cora N. Sternberg, MD, FACP, chief of the department of medical oncology at the San Camillo and Forlanini Hospitals in Rome, and colleagues sought to evaluate whether immediate adjuvant cisplatin-based combination chemotherapy improved outcomes in patients with pT3 to pT4 and/or node-positive M0 urothelial carcinoma of the bladder.
Cora N. Sternberg
The analysis included 284 patients. Researchers assigned 141 patients to immediate adjuvant treatment with four cycles of gemcitabine (Gemzar, Lilly) plus cisplatin, high-dose methotrexate, vinblastine, doxorubicin and cisplatin. The other 143 patients received six cycles of deferred chemotherapy at the time of relapse.
Ninety-one percent of patients in the immediate treatment arm started treatment, and 45% of patients in the deferred treatment arm received chemotherapy at the time of disease progression. An additional 2% of patients in the deferred group requested immediate chemotherapy.
Median follow-up was 7 years (interquartile range [IQR], 5.2-8.7). By this time, 47% of patients had died in the immediate treatment arm and 57% had died in the delayed treatment arm.
Overall, immediate adjuvant chemotherapy was not associated with improved OS (adjusted HR=0.78; 95% CI, 0.56-1.08).
However, patients who underwent immediate chemotherapy demonstrated significantly extended PFS (HR=0.54; 95% CI, 0.4-0.73). More patients who received immediate vs. delayed chemotherapy achieved 5-year PFS (47.6% vs. 31.8%).
More patients in the delayed chemotherapy arm experienced grade 3 to grade 4 myelosuppression (35% vs. 26%), neutropenia (53% vs. 38%) and thrombocytopenia (38% vs. 28%). One patient in each arm died due to toxicity.
“This trial … is limited in sample size and power for assessing its primary endpoint, OS,” Sternberg and colleagues wrote. “The results showed, however, a significant increase in PFS. Taken together with other similar studies, the results suggest that adjuvant chemotherapy might increase survival, at least in some subgroups of patients that this study alone cannot identify.”
Nodal status might provide an indication as to which patients will benefit from adjuvant chemotherapy, Arlene O. Siefker-Radtke, MD, and Jianjun Gao, MD, PhD, of The University of Texas MD Anderson Cancer Center, wrote in an accompanying editorial.
“Results of Sternberg and colleagues’ study suggest that adjuvant chemotherapy might benefit patients with node-negative disease,” Siefker-Radtke and Gao wrote. “However, most patients in this trial did not have adequate lymph-node dissection, so this finding should be interpreted with caution. An alternative conclusion is that patients with inadequate lymph-node dissection might be more likely to benefit from adjuvant chemotherapy. Also, many of these patients might have been characterized as node-positive if more lymph nodes had been removed. Clearly, additional studies are needed to confirm this finding.”
For more information:
Siefker-Radtke AO. Lancet Oncol. 2014;doi:10.1016/S1470-2045(14)71187-8.
Sternberg CN. Lancet Oncol. 2014;doi:10.1016/S1470-2045(14)71160-X.
Disclosure: The study was funded in part by Lilly. See the study for a list of the researchers’ relevant financial disclosures.