Liu, Heshan

188 Background: Unplanned subgroup analyses from several studies have suggested primary tumor sidedness (PTS) as a potential prognostic and predictive parameter in metastatic colorectal cancer (mCRC). We aimed to investigate the prognostic and predictive impact of PTS on outcomes. Methods: PTS data of 7,828 mCRC patients (pts) from 10 first-line randomized trials in the ARCAD database were pooled. PTS was defined as right-sided (RS) or left-sided (LS) if tumor arose from the cecum to the hepatic flexure or from the splenic flexure to the rectum, respectively; transverse colon cancers were not included. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox models adjusting for age, sex, performance status (PS), prior radiation/chemo, and stratified by treatment arm. Predictive value was tested by interaction term between PTS and treatment (anti-EGFR plus chemotherapy vs. chemotherapy alone). Results: Compared to RS pts (2407, 31%), LS pts (5421, 69%) had better OS (median: 21.6 v 16.8 mos; HRadj: 0.73, 95% CI 0.69-0.78, P < .001) and PFS (median 8.4 v 7.2 mos; HRadj: 0.81, 95% CI 0.76-0.86, P < .001). Results were consistent among subgroups defined by age, sex, PS, metastatic sites and chemo backbone (irinotecan- and oxaliplatin-based). Interaction between PTS and KRAS mutation was significant (Pinteraction< .001): LS is associated with better prognosis only among KRAS wild-type (wt) (HRadj: OS 0.62, 95% CI, 0.55-0.70; PFS 0.71, 95% CI 0.63-0.80), but not among KRAS mutated pts. Among KRAS wt pts, survival benefit from anti-EGFR was observed for LS, but not for RS (table). Conclusions: The prognostic value of PTS is restricted to the KRAS wt population. PTS is predictive of anti-EGFR efficacy, with a significant improvement of survival for LS mCRC pts. These results suggest treatment stratification in mCRC studies by both PTS and KRAS status. [Table: see text]

BACKGROUND: Historically, one in five Hodgkin Lymphoma (HL) patients treated with bleomycin develop bleomycin pulmonary toxicity (BPT), a life-threatening interstitial pneumonitis. The current treatment paradigm consists of prompt discontinuation of bleomycin, administration of corticosteroids, antibiotics, hospital admission, respiratory therapy, or intensive care. BPT represents a challenge for patients with HL as it not only impairs respiratory function, but also has negative impacts on clinical outcomes. A collection of a dozen studies suggest BPT has a mortality rate just short of 10% of patients who develop BPT. Given recent data on bleomycin omission with negative interim PET scan, we assessed changes in BPT rates and severity over the past 15 years. Overall, treatment protocol characterization and patient characteristics most responsive to BPT treatment are poorly understood. OBJECTIVES: In this study, we investigated the clinical impact and treatment strategies in patients with BPT. Our goals were to: 1) Identify HL patients in the last decades who developed BPT and identify risk factors for BPT, 2) evaluate the impact of BPT on long-term clinical outcomes, and 3) characterize patterns of treatment strategies among patients with HL who develop BPT. METHODS: A single-center, retrospective analysis was preformed using patient data from the Mayo Clinic Lymphoma Database (Rochester, MN) consisting of 1,299 patients diagnosed with HL. All patients were diagnosed between 2003-2018. Inclusion criteria included 1) newly diagnosed, biopsy proven HL, 2) upfront treatment with ABVD, 3) treatment was received at our institution. All patients were assessed for clinically relevant HL characteristics including stage of disease, presence of bulky disease, presence of B symptoms, Eastern Cooperative Oncology Group (ECOG) performance status, BPT risk factors, and bleomycin treatment regimen. BPT was clinically defined as 1) Presence of pulmonary symptoms, 2) bilateral interstitial infiltrates on imaging, and 3) no evidence of infectious etiology. Patients treated in the "Early Era" (2000s) were compared to patients in the "Recent Era" (2010s). Comparison of continuous variables between BPT groups was assessed with Wilcox rank-sum test. OS and PFS were estimated via the Kaplan-Meier method. Approval of the protocol by the Mayo Clinic Institutional Review Board (IRB) was obtained and all patients were consented accordingly. RESULTS: One-hundred twenty six patients met the inclusion criteria for this study. Median follow-up for PFS and OS was 5.5 years (95%CI = 4.8-6.4) and 5.8 years (95%CI = 5.0-7.0), respectively. The 10-year OS and PFS among all patients were 85.1% (95%CI = 77.8-93.1) and 86.3% (95%CI = 80.1-93.0), respectively. Forty-seven patients (37% of all patients) met criteria for BPT. The estimated 10-year OS for BPT and non-BPT patients were 74.7% (95%CI = 61.8-90.5) and 91.7% (95%CI = 83.9-100.0), respectively. The estimated 10-year PFS for BPT and non-BPT patients were 84.7% (95%CI = 74.8-95.8) and 87.0% (95%CI = 79.1-95.8), respectively. In univariable analysis, BPT negatively impacted OS (HR=3.6, 95%CI: 1.2-10.6). However, bleomycin omission did not impact OS (HR=1.3, 95%CI=0.5-3.7). BPT-mortality was 17%. In multivariable analysis, BPT was not significantly associated with OS after adjusting for baseline characteristics (HR=3.0, 95%CI=0.9-9.9). Patients were older (median: 46 vs 33 years) and received less bleomycin (median: 107 vs 215 units) compared to non-BPT patients. BPT was most often managed with bleomycin omission with 59% of patients (74 of 126 patients) having omitted bleomycin at some point during treatment. Patients treated in the "Recent Era" (2010s) had lower BPT rates (28% vs 48%), mortality (10% vs 21%), bleomycin dose (143 vs 204 units), and bleomycin cycles (7 vs 12 cycles), yet higher prophylactic bleomycin omission (59% vs 8%) compared to "Early Era" (2000s). Patients treated in the Recent Era compared to Early Era had a reduction of BPT treatment with steroids, hospital admission, respiratory therapy, and ICU admission by 12%, 22%, 14%, 13%, respectively. CONCLUSION: Overall, our data suggests BPT continues to impact OS in HL patients treated with ABVD, however BPT treatment is decreasing as management changed in recent years. Disclosures Ansell: Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding.

PURPOSE Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years. PATIENTS AND METHODS Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician’s choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS. RESULTS The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56% and 50%, respectively (hazard ratio [HR], 0.80; P = .03); breast cancer–specific survival rates were 88% and 82%, respectively (HR, 0.62; P = .03); and overall survival rates were 62% and 56%, respectively (HR, 0.84; P = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor–negative patients (HR, 0.66; P = .02), but not among hormone receptor–positive patients (HR, 0.89; P = .43). Overall, 43.9% of patients have died (13.1% from breast cancer, 16.4% from causes other than breast cancer, and 14.1% from unknown causes). Second nonbreast cancers occurred in 14.1% of patients. CONCLUSION With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor–negative disease. Competing risks in this older population dilute overall survival benefits.

533 Background: Current guidelines define TNBC as complete absence of estrogen (ER) and progesterone receptor (PR), without HER2 amplification. However, the prognostic impact of clinical and histopathological factors, sTILs, and AdjCT in TNBC meeting these strict criteria is unknown. Methods: From a cohort of 9985 women who underwent upfront surgery for M0 breast cancer (BC) at Mayo Clinic Rochester from 1985-2012, 1159 pts with ER negative or low (≤10%) BC were identified for central ER/PR/HER2 staining and HER2 FISH (IHC2+ only) to select those with TNBC by modern definitions. Cox proportional hazards models were used to assess the impact of clinicopathological variables on invasive disease-free (IDFS) and overall survival (OS). Results: Tumors from 605 pts (median age 56.3 yrs) met criteria for TNBC (ER < 1%, PR < 1% and HER2 0, 1 or 2+ and FISH negative). 51% were T1, 65% N0, 88% grade 3, and 75% had Ki67 > 15%. Histologically, 39% were anaplastic, 26% invasive ductal, 16% medullary, 8% metaplastic, 6% apocrine and 5% others. Median sTILs was 20% (0-90%). 55% pts received AdjCT [21% anthracycline (A), 19% A + taxane, and 15% other]. Median follow-up for IDFS and OS were 7.4 and 10.6 yrs, respectively. Multivariate analyses demonstrated that higher N stage (p < 0.01), lower sTILs (p = 0.01) and no AdjCT (p < 0.01) were independently associated with worse IDFS and OS. Histology (medullary subtype) was associated with better IDFS in univariate (HR 0.56, 95% CI, 0.35-0.89) but not in multivariate analyses, once sTILs were accounted for. Among systemically untreated pts (n = 182), higher N (p < 0.01) and lower sTILs (p = 0.04) were associated with worse IDFS. For systemically untreated T1N0 pts (n = 111), the 5-yr IDFS was 70% (95% CI, 61-81) [T1a: 83% (95% CI, 63-100), T1b: 68% (95% CI, 52-88) and T1c: 67% (95% CI, 55-83)], compared to 78% (95% CI, 68-84) for T1N0 pts treated with AdjCT. Conclusions: In TNBC pts, N stage, sTILs and receipt of AdjCT were independently prognostic for IDFS and OS. sTILs remained prognostic for IDFS in systemically untreated TNBC. In N0 TNBC, the risk of recurrence or death was substantial in the absence of chemotherapy, even for those with T1 tumors.