Hepatosplenic γ-δ T-cell lymphoma, an exceptionally uncommon subtype of peripheral T-cell lymphomas, commonly presents with advanced-stage disease manifesting with hepatosplenomegaly, cytopenias, and constitutional symptoms. Management of this subset is challenging as a result of the unique presentation and refractory nature to conventional treatment approaches. There is a lack of consensus guidelines for up-front induction strategies, and the role of consolidative autologous or allogeneic stem-cell transplantation is controversial. Prospective studies are lacking, and treatment is often guided by literature on the basis of case series or single-institution studies, lending to expert opinions influencing treatment paradigms.

Idoxifene was both active and well tolerated in postmenopausal women with metastatic breast cancer. Idoxifene had similar efficacy and toxicity to tamoxifen in this randomized comparison.

Tumor profiling and targeted therapy revolutionized the treatment strategies of metastatic colorectal cancer (mCRC) in the last decade. The heterogeneity of CRC tumors plays a critical role in the development of treatment resistance, which underscores the need to understand the molecular mechanism involved in CRC to develop novel targeted therapeutic strategies. This review provides an overview of the signaling pathways driving CRC, the existing targeted agents, their limitations, and future trends.

12028 Background: Clinical trials leading to the approval of immune checkpoint inhibition (ICI) have almost exclusively been performed in patients with good performance status (ECOG PS of 0-1). However, ICI remains an attractive option for patients with advanced tumors and poor performance status, considering their overall tolerability. While use of ICI in patients with poor PS (ECOG PS of 2 or greater) has been rapidly adopted, whether these patients derive the same benefits as expected in the studied populations is largely unknown. We therefore performed an institutional retrospective analysis of all patients treated with palliative single agent anti-PD1 or anti-PDL1 to determine response and survival for those with poor performance status. Methods: We retrospectively identified patients with advanced solid tumor malignancies who were treated with ICI monotherapy with palliative intent at our institution between 2015-2019. The primary objective was to compare overall survival (OS) for patients with good PS (ECOG PS 0-1) with those with poor PS (ECOG PS 2 or 3-4). The log-rank test compared the survival among patients with different ECOG PS. In addition, we used a proportional hazards model to assess association between ECOG PS and the OS with adjustment for age, gender, and smoking status. A secondary objective was to compare overall response rates (ORR) of the three ECOG PS groups which were evaluated with a binary rate model. Results: We identified 266 patients treated with ICI, 87 with NSCLC, 34 with melanoma, 33 with RCC, 24 with bladder cancer, 22 with head/neck cancer, and the rest with other histologies. 187 (70%) were ECOG PS 0-1, 62 (23%) were ECOG PS 2, and 17 (7%) were ECOG PS 3-4. 89 of these patients (33%) were still alive at time of last follow-up. Across all tumor types, patients with ECOG PS 0-1 had superior survival compared to ECOG PS 2 (median survival 12.4 months vs 4.6 months, HR 0.41, p < 0.001). Median survival for ECOG PS 3-4 was lower at 2.3 months. The ORR for ECOG PS 0-1 (23%) was significantly higher to that of ECOG PS 2 (6%, p = 0.02). ORR for ECOG PS 3-4 was 12%. Conclusions: Despite the appeal of ICI for patients with advanced malignancy and poor performance status, outcomes were poor. Survival and objective response rates for patients with ECOG PS 2 and higher were significantly worse than those with ECOG PS 0-1. ICI treatment comes with cost, including potentially forgoing early hospice referral or optimal support at the end of life. Prospective trials defining the activity and role of ICI in poor PS are urgently needed.

PURPOSE Clinical trials, which led to the approval of immune checkpoint inhibitors (ICI), have been almost exclusively performed in patients with good Eastern Cooperative Oncology Group performance status (ECOG PS of 0-1). However, ICI remains an attractive option for patients with advanced tumors and poor PS. We hypothesized that patients with ECOG PS ≥ 2 would have worse outcomes with ICI. METHODS We retrospectively identified patients with advanced solid tumors who were treated with ICI at our institution. The log-rank test compared the survival among patients with different ECOG PS. We used a proportional hazards model to assess association between ECOG PS and overall survival (OS) with adjustment for covariates including age, sex, malignancy type, time from advance disease diagnosis, and line of therapy. We compared overall response rates between groups with Pearson chi-square exact test. We also analyzed in-hospital mortality and hospice referral rates. RESULTS We identified 257 patients treated with ICI. One hundred eighty-two patients had ECOG PS 0-1, and 75 had ECOG PS ≥ 2. The median overall survival was 12.6 months for the ECOG PS 0-1 group compared with 3.1 months for the ECOG PS ≥ 2 group ( P < .001). The overall response rate for patients with ECOG PS 0-1 was 23% compared with 8% for those with poor PS ( P = .005). Patients with poor PS treated with ICI had similar hospice referral rates (67% for ECOG PS ≥ 2 v 61.9% for ECOG PS 0-1, P = .50) but were more likely to have in-hospital death as compared with the good PS group (28.6% v 15.1%, P = .035). CONCLUSION Despite the appeal of ICI in patients with advanced malignancy and poor PS, outcomes in this cohort were poor. Prospective trials defining the activity and role of ICI in poor PS are urgently needed.