BACKGROUNDEnzalutamide and abiraterone are new androgen-axis disrupting treatments for metastatic castration resistant prostate cancer (mCRPC). We examined response and outcomes of enzalutamide-treated mCRPC patients in the real-world context of prior treatments of abiraterone and/or docetaxel.METHODSWe conducted a seven-institution retrospective study of mCRPC patients treated with enzalutamide between January 2009 and February 2014. We compared baseline characteristics, PSA declines, PSA progression-free survival (PSA-PFS), duration on enzalutamide, and overall survival (OS) across subgroups defined by prior abiraterone and/or docetaxel.RESULTSOf 310 patients who received enzalutamide, 36 (12%) received neither prior abiraterone nor prior docetaxel, 79 (25%) received prior abiraterone, 30 (10%) received prior docetaxel, and 165 (53%) received both prior abiraterone and prior docetaxel. Within these groups, respectively, ≥30% PSA decline was achieved among 67%, 28%, 43%, and 24% of patients; PSA-PFS was 5.5 (95% CI 4.2–9.1), 4.0 (3.2–4.8), 4.1 (2.9–5.4), and 2.8 (2.5–3.2) months; median duration of enzalutamide was 9.1 (7.3-not reached), 4.7 (3.7–7.7), 5.4 (3.8–8.4), and 3.9 (3.0–4.6) months. Median OS was reached only for patients who received both prior abiraterone and docetaxel and was 12.2 months (95% CI 10.7–16.5). 12-month OS was 78% (59%–100%), 64% (45%–90%), 77% (61%–97%), and 51% (41%–62%). Of 70 patients who failed to achieve any PSA decline on prior abiraterone, 19 (27%) achieved ≥30% PSA decline with subsequent enzalutamide.CONCLUSIONSThe activity of enzalutamide is blunted after abiraterone, after docetaxel, and still more after both, suggesting subsets of overlapping and distinct mechanisms of resistance.

BACKGROUND. Limited data are available on the management of glioma in pregnant women. Therefore, the aim of the current article was to describe the outcome of women with malignant gliomas who were exposed to chemotherapy early in the gestation period of their pregnancies. METHODS. The authors presented a case series of 6 women with malignant gliomas who during glioma‐directed treatment were discovered to have an unplanned pregnancy. All patients elected to discontinue chemotherapy and carry their pregnancy to term. RESULTS. All women had uneventful pregnancies with no glioma‐related complications. All women delivered healthy newborns without evidence of congenital malformations despite exposure to cytotoxic chemotherapy and anticonvulsant medications. CONCLUSIONS. Management of malignant glioma during pregnancy is challenging; however, normal delivery and healthy live birth is possible. Cancer 2008. © 2008 American Cancer Society.

18 Background: Enzalutamide (Enza) and abiraterone (Abi) are next generation hormonal agents for metastatic castration resistant prostate cancer (mCRPC). Whether these agents can be effectively sequenced is not yet well understood. Results of retrospective analyses of Abi after prior Enza have demonstrated modest responses of brief duration, suggesting common resistance pathways. Here, we retrospectively analyze response to Enza with or without prior Abi treatment. Methods: We retrospectively reviewed 195 patients from seven academic centers treated with Enza between January 2009 and August 2013. Data were collected on disease characteristics, prior therapies, and prostate-specific antigen (PSA) values at baseline and while on treatment. Logistic regression was used to evaluate association between 30% or greater PSA decline on Enza and either prior Abi treatment or 30% or greater PSA decline on prior Abi after accounting for potential confounders. Results: One hudred eighty three patients had non-missing PSA starting and nadir values on Enza, with starting PSA median 102.0 (range 1.1–5007.0) ng/mL. Overall, 42% (76 of 183) of Enza-treated patients achieved a 30% or greater PSA decline, with 39% (58 of 150) response among prior Abi-treated patients and 55% (18 of 33) response among Abi-naïve patients. Of 79 patients who lacked significant response to prior Abi, 30% (25 of 79) achieved a 30% or greater PSA decline and 19% (15 of 79) achieved a 50% or greater PSA decline with subsequent Enza. Odds of achieving a 30% or greater PSA response on Enza was 2.3 times higher for Abi-naïve patients versus prior Abi-treated patients (95% CI 1.0–5.5, P=0.06) and 1.9 times higher for Abi-responders vs Abi-non-responders (95% CI 1.0–3.7, P=0.06) after adjusting for prior docetaxel and concurrent steroid use. Conclusions: In this multi-center retrospective study, 39% of patients achieved a 30% or greater PSA decline with Enza after prior Abi treatment. While the activity of Enza appears to be blunted in the post-Abi setting, PSA declines still occur in a meaningful proportion of patients. Notably, 30% of patients without significant response to prior Abi responded to subsequent treatment with Enza, suggesting a subset of men with distinct biological resistance pathways. Data will be updated at the time of presentation.