Start Of Targeted Therapy Research Articles

Outcomes of melanoma soft parts/clear cell sarcoma (MSP/CCS) patients (pts) with immune and targeted therapies.

e21046 Background: Overall survival (OS) for pts with cutaneous melanoma has vastly improved with checkpoint inhibitors (CPI) and targeted therapy (TT), but less is known about outcomes of other rare tumors showing melanocytic differentiation. We examined outcomes for metastatic pts with MSP/CCS at MD Anderson (MDA) to characterize outcomes with contemporary therapies. Methods: Pts with MSP/CCS were identified in the MDA databases. Pts with < 2 visits to MDA or without molecular confirmation of dx were excluded. Log-rank testing was used to compare OS among distributions. Results: A total of 102 MSP/CCS pts were identified. Initial diagnosis was local disease 46%, regional metastases 34%, and systemic metastases 20%. Primary tumor site was lower extremity (LE) 48%, GI tract 29%, upper extremity (UE) 18%. 65 pts were diagnosed with metastatic disease (dz), including 32% with lung-only, 14% liver-only, and 51% with multiple metastatic sites. Median OS from diagnosis of distant metastatic dz was 22 mos (95% CI 16-34 mos). Primary tumor site (GI 46.4 vs. LE 19.1 vs. UE 14.7 mos; p = 0.018) and race (white 26.8 vs. black 6.5 mos, p = 0.019, HR 0.45) were significantly associated with OS from distant metastasis; sex, age, decade of diagnosis, size of primary, and prior treatment with neoadjuvant or adjuvant therapy were not. Treatments for metastatic dz included chemotherapy (n = 29), biochemotherapy (n = 11), biotherapy (n = 5), CPI (n = 11) and TT (n = 19). Median OS was 15.9 mos from start of CPI (range 10.7 to NR) and 16.9 mos from start of TT (range 7.8 to NR). Median OS from metastatic dz for pts not treated with CPI or TT was 17.1 mos (range 12.4 to 32.5), which was not significantly different versus CPI or TT. Duration of response was < 6 mos for 91% pts receiving CPI and 89% pts receiving TT. One pt had a durable response (41.8 mos) to anti-PD1 and one pt had a durable response (24.8 mos) to an AKT inhibitor. Conclusions: While rare responses to CPI and TT were observed, no significant difference was detected in OS compared to traditional therapies in pts with metastatic MSP/CCS. The development of more effective therapies remains an unmet need for this disease.

Effect of hematologic improvement (HI) on survival in patients (pts) given targeted therapy (TT) as initial treatment of acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS)

7059 Background: Recent years have seen the introduction of TT for pts with AML and HR- MDS (> 10% marrow blasts). New criteria, less stringent than those for CR, for response to these agents have been promulgated, giving rise to the response category HI. However, the effect of achieving HI on survival is uncertain. Methods: 180 pts, median age 73, with AML or HR-MDS received TT, most commonly decitabine (69 pts), from 2000–2006. Treatment-related death occurred in 11%, CR in 28%, CRp in 6%, and 55% (99 pts) were resistant. We examined survival in these 99 according to whether TT produced HI, blood count criteria for which were as defined by the International Working Group (IWG) for MDS. Initially, we, unlike the IWG, did not require any duration of HI, however; in subsequent analyses, we required durations of = 4 weeks (HI-4) and, like the IWG, = 8 weeks (HI-8). Results: Survival time dated from start of TT was similar in the 32 pts who achieved HI and the 67 who did not. However, the 13 pts with HI-8 lived longer than those with shorter or no HI (48% vs. 11% at 2 years, p=0.01) as did the 14 with HI-4 (p=0.01). Because HI-4 and HI-8 pts had to live long enough to achieve and maintain HI, we re-did the analysis including only the 84 pts who lived = 67 days from start of TT, the median time needed to observe HI-4. This analysis, which included HI-4, age, and cytogenetics as predictors of survival, indicated that HI-4 was the strongest predictor of longer survival (HR 0.34, 95% CI 0.13–0.86, p=0.02). Results were analogous when we limited the analysis to the 68 pts who lived at least 138 days, by which time 75% of HI-4 pts had achieved HI (p=0.06). Conclusions: Our results suggest that HI-4 (or HI-8 as defined by the IWG) following TT confers a survival benefit in AML or HR-MDS. No significant financial relationships to disclose.