Heavy appetizer.

Top Line: You’re probably familiar with the OUTBACK trial—no, not the one where you see if you can handle both the bloomin’ onion and the aussie cheese fries in one sitting—we’re talking about the trial randomizing observation or adjuvant chemo after definitive chemoradiation for locally advanced cervical cancer.
The Study: The rationale for that trial is that a large proportion of those patients suffer distant failure. With a similar rationale, some ask whether neoadjuvant chemo (NAC) could improve survival outcomes in this population. This phase 2 trial from Brazil randomized over 100 women with FIGO IIB to IVA cervical cancer to standard chemoradiation +/- NAC. NAC consisted of gemcitabine and cisplatin every 3 weeks for 3 cycles. Chemoradiation consisted of 45-50.4 Gy pelvic radiation with weekly cisplatin generally followed by intracavitary brachytherapy (7-7.5 Gy x 4 fractions). At 3 years, the primary endpoint of progression-free survival was significantly worse with NAC, dropped from 60 → 41%. Surprisingly, overall survival was also significantly worse with NAC, reduced from 87 → 61%. Didn’t see that coming. Why the difference? On the one hand, starting NAC and delaying definitive chemoradiation could start the tumor clock ticking in a disease that is known to be sensitive to total treatment time. Indeed, complete responses were much less common with NAC. On the other hand, it could also impair delivery of the treatment most likely to cure the patient in the first place, definitive chemoradiation.
TBL: Neoadjuvant gem/cis is associated with worse progression-free and overall survival among patients receiving definitive chemoradiation for locally advanced cervical cancer. | da Costa, J Clin Oncol 2019


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