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Advanced lung adenocarcinoma patients treated with ganetespib in combination with docetaxel had an acceptable safety profile. While the study's primary end points were not met, significant prolongation of PFS and OS was observed in patients >6 months from diagnosis of advanced disease, a subgroup chosen as the target population for the phase III study.

Background Providing oncology services during a pandemic can contribute to mental health challenges among healthcare workers. The present study aimed to evaluate the levels of depression, anxiety, and stress in healthcare and administrative staff in 5 oncology institutions in Bosnia and Herzegovina (BiH) in 2020 during the coronavirus disease 2019 (COVID-19) pandemic using the Depression, Anxiety and Stress Scale (DASS-21) questionnaire. Material/Methods A cross-sectional observational study enrolled 175 healthcare and administrative workers from 5 oncology institutions in BiH during December 2020. Data were collected using a questionnaire that captured general information about the participants and a DASS-21 questionnaire. Results Statistical analysis revealed a statistically significant difference in the levels of depression, anxiety, and stress ( P =0.003, P =0.011, and P =0.022, respectively) among participants with comorbidities connected with increased risk of severe illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared with participants without comorbidities. There was also a statistically significant difference in the levels of stress among participants from different cities ( P =0.031). Supplement intake and educational level were significantly related ( P =0.012). High levels of stress and anxiety were accompanied by high levels of depression among participants ( P <0.01). Conclusions The findings from the present study showed that the COVID-19 pandemic has had an effect on depression, anxiety, and stress levels in oncology staff in BiH. Monitoring these levels and providing interventions and support to oncology staff are increasingly important for their wellbeing and retention at a time of global crisis in healthcare.

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Adverse drug reactions still pose an important clinical problem. Dihydropyrimidine dehydrogenase (DPD) is an enzyme that regulates 5-FU quantities available for anabolic processes and hence affects its pharmacokinetics, toxicity and efficacy. There are several studies describing a hereditary (pharmacogenetic) disorder in which individuals with absent or significantly reduced DPD activity may even develop a life-threatening toxicity following exposure to 5-FU. The most common mutation is known as the DPYD*2A or as the splice-site mutation (IVS14 + 1G A) leading to creation of a dysfunctional protein. An objective behind the study was to ascertain existence of the IVS14 + 1G A mutation among the population of Bosnia and Herzegovina. Our research has undeniably attested to existence of one heterozygote for the DPYD gene mutation, i.e. one heterozygote for IVS14 + 1 G > A, DPYD*2A mutation.

571 Background: Capecitabine (Xeloda [X]) and docetaxel (Taxotere [T]) are highly active single agents in MBC. The XT combination leads to superior overall survival (OS), time to progression (TTP) and response rate (RR) vs. T alone in anthracycline-preatreated MBC [O’Shaughnessy et al. J Clin Oncol 2002], although only one third of pts in the T group received X after progression. We designed this study to determine whether XT is better than sequential T→X in first-line MBC. Methods: 100 pts with measurable MBC, prior adjuvant anthracyclines (100%) but no prior chemotherapy for MBC and KPS ≥70 received 3-weekly cycles of either XT (X 1250mg/m2 bid d1–14 + T 75mg/m2 d1) or T→X (T 100mg/m2 d1 followed after progression by X 1250mg/m2 bid d1–14). X monotherapy data were not considered in the RR or TTP analyses but were included for OS and safety. Results: The XT and T→X arms were well balanced for prognostic factors: median age 48 (29–59) vs. 51 (31–64) years; median KPS 100 (70–100) in both arms; hormone-responsive disease 20 vs. 16%; dominant metastatic sites (liver 42 vs. 44%, lymph nodes 34 vs. 36%, lung 28 vs 24%, bone 20 vs 18%); number of involved organs (1 = 58 vs. 52%, >1 = 42 vs. 48%); median interval since prior adjuvant anthracyclines (18.5 vs. 17.0 months). Efficacy findings are shown in the table . 74% of the pts in the T→X arm crossed-over to X on progression. The post-study treatment rate was similar in both arms. The most common grade 3/4 adverse events (>5% of pts) with XT vs. T→X were: hand-foot syndrome 18 vs. 4%; stomatitis 16 vs. 8%; neutropenia 12 vs. 14%; neutropenic fever 12 vs. 14%; diarrhea 12 vs. 8%; fatigue 8 vs. 12%; alopecia 6 vs. 8%; edema 4 vs. 8%. Dose reductions were necessary for 52% of pts on XT and 36% of pts on T→X. Conclusions: XT provides significant RR, TTP and OS advantages over T→X. XT should be the standard therapy in fit poor-prognosis pts with aggressive disease. [Table: see text] No significant financial relationships to disclose.

CRA8007 Background: Heat shock protein 90 chaperone function is critical for the biological effects of several oncoproteins. Ganetespib (G) is a highly potent 2nd-generation Hsp90 inhibitor with a favorable safety profile and single-agent clinical activity. Methods: Based on synergistic preclinical interactions between docetaxel (D) and G, we conducted a randomized (1:1), international open-label study of D with or without G. Patients with advanced lung adenocarcinoma, one prior systemic therapy, and ECOG PS 0/1 were included. D was given at 75 mg/m2 on day 1 of a three-week cycle. In the experimental arm, D was given on day 1 and G at 150 mg/m2 on days 1 and 15. The co-primary endpoints were PFS in patients with elevated LDH (eLDH) levels, or tumors harboring KRAS mutations. Key secondary endpoints were OS and PFS in all adenocarcinoma patients. Target enrollment was 240 adenocarcinoma, 120 eLDH, and 80 mKRAS patients. Statistical tests are 1-sided. Results: Enrollment of 255 adenocarcinoma patients completed in November 2012; results are reported for this population. Patient characteristics were balanced (median age 60 years, males ~60%, PS 0 ~40% and never-smoker ~25%). For D+G vs. D the median number of cycles delivered was 5 vs. 4; the grade 3/4 adverse events were neutropenia 38% vs. 37%; fatigue 4% vs. 3%; anemia 7% vs. 6%; diarrhea 3% vs. 0; fever with neutropenia 8% vs. 2%. At the time of abstract submission OS HR was 0.69 (90% CI 0.48 to 0.99, p=0.093), the PFS HR was 0.70 (90% CI 0.53 to 0.94, p=0.012), and the ORR was 15% vs 11%, favoring D+G. For patients that were enrolled >6 months after diagnosis of advanced NSCLC (N=175; 69%), a prespecified stratification factor, the OS HR was 0.41 (90% CI 0.25 to 0.67, p=0.0009), the PFS HR was 0.47 (90% CI 0.32 to 0.69, p=0.0005), and the ORR was 16% vs 12%. Updated results for both populations above, as well as for the eLDH and mKRAS subsets, will be presented. Conclusions: D+G demonstrated improvement in OS, PFS, and ORR over D alone for second-line therapy of lung adenocarcinoma. A phase III study in second-line advanced adenocarcinoma patients (> 6 months from diagnosis) is ongoing (GALAXY-2). Clinical trial information: NCT01348126.

CRA8007 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.