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e23501 Background: Giant cell tumor of bone (GCT) is a relatively rare, benign but locally aggressive osteolytic skeletal neoplasm of young adults, most frequently occurs at the epiphysis of long bones. Distant metastases occur approximately 2-6% of cases most often to the lungs. However, pulmonary metastases do not carry the same connotation as metastases associated with malignant tumors, such as lung cancer or sarcoma. Rarely, GCT undergoes true malignant transformation. The aim of this study is to analyze the clinical behavior of advanced GCT during long-term observer in N.N. Blokhin National Medical Research Center of Oncology. Methods: We observed 51 advanced cases among 298 GCT from 2005 till 2020 in N.N. Blokhin National Medical Research Center of Oncology. Disease was histologically confirmed by a sarcoma pathologist. Patients underwent CT/MRI every 2 or 3 months of treatment and every 3, 6 or 12 months of follow up period. Treatment options were included atypical pulmonary resection, palliative surgery, chemotherapy with CAP or AI combination, interferon alfa or observation until progression. After 2013 prefer treatment option for advanced GCT was denosumab with once in 3 month’s regimen after 2 years monthly therapy. All patients received daily calcium and vitamin D supplement. Logistic regression was using for statistic analyzes. Results: Median follow-up was 45 months. The average age of patients was 34,8 years, and the women and men ratio was about 1,8:1. The most commonly affected sites were tibia (23,5%, 12/21), sacrum (17,6%), radius (13,7%) and femur (9,8%). According Campanacci classification G3 was the most commonly grade (90%). 46 (56%) cases were anatomically compounded due to tumor localization and 19 (37%) cases were primary disease. 18/298 (6%) cases were with pulmonary metastases. Surgery in history (p < 0,001) and tumor localization in extremity (p < 0,001) were significant for metastasis development. The primary malignant GCT observed in 1% (3/298) cases and 1 % cases of malignant transformation GCT into sarcoma. Only 1/51 (1,9%) death was observed in advanced GCT group. Complications ≥3 grade were observed only in pre-denosumab era. Conclusions: In this study we showed long-term observation of advanced GCT and evaluated significant factors for metastasis development. Surgeries in history and tumor localization were associated with higher risk of metastasis. Denosumab for advanced GCT is a choice of treatment, we wasn’t observed any cases of GCT malignant transformation during denosumab treatment. Quality of live was better in compare with pre-denosumab era. Further investigation of long term denosumab complications is awaited.

5517 Background: In ARIEL4 (NCT02855944), rucaparib significantly improved the primary endpoint of progression-free survival (PFS) vs chemotherapy (CT) in patients with advanced, relapsed ovarian carcinoma (OC) harboring a deleterious BRCA1/2 (BRCA) mutation (median PFS 7.4 [95% CI 7.3–9.1] vs 5.7 [5.5–7.3] months; hazard ratio (HR) 0.64 [95% CI 0.49–0.84]; P=0.001). This prespecified exploratory analysis investigated the effect of platinum sensitivity on the efficacy of rucaparib vs CT in ARIEL4. Methods: Patients were randomized 2:1 to oral rucaparib 600 mg twice daily or CT and stratified based on progression-free interval (≥1 to 2; patients with fully platinum-sensitive disease received investigator’s choice of platinum-based CT (single-agent carboplatin or cisplatin, or platinum doublet). Patients could crossover from CT to rucaparib following radiologic disease progression. Efficacy endpoints were explored in patients with a confirmed BRCA mutation (patients with a reversion mutation were excluded), based on the randomization strata of platinum sensitivity. Results: The visit cutoff date was September 30, 2020. PFS and objective response rates (ORR) per RECIST v1.1 for rucaparib vs CT across subgroups are presented in the Table. The most common treatment-emergent adverse events in the rucaparib group were anemia/decreased hemoglobin (platinum-resistant patients: rucaparib 47% vs CT 40%; partially platinum-sensitive patients: 63% vs 27%; fully platinum-sensitive patients: 58% vs 20%) and nausea (52% vs 21%; 51% vs 23%; 60% vs 68%). In the intent-to-treat population, 74/116 (64%) patients in the CT group crossed over to receive rucaparib: 39/59 (66%) with platinum-resistant, 25/31 (81%) with partially platinum-sensitive, and 10/26 (38%) with fully platinum-sensitive disease. Conclusions: Results from this exploratory subgroup analysis suggest that rucaparib is a reasonable treatment option for heavily pretreated patients across all platinum sensitivity subgroups. Safety was consistent with prior rucaparib studies. Clinical trial information: NCT02855944. [Table: see text]

11521Background: Giant cell tumor of bone (GCT) is a relatively rare, benign but locally aggressive osteolytic skeletal neoplasm of young adults. This study is non-interventional observational GCT treatment study in the Russian Federation (RF). Designed to detect epidemiology data as well as the clinical efficiency of surgical and/or denosumab (Db) treatment of GCT in the RF. Methods: Between August 2016 and October 2017, 112 adult patients (pts) with GCT were enrolled. Ten Russian Cancer Center are included in this study. The primary endpoint was Time-To-Progression (TTP). Adult and skeletally mature adolescent pts with resectable and unresectable GCT (N = 54) received subcutaneous Db 120 mg every 4 weeks with a loading dose of 120 mg SC on study days 8 and 15. Options for surgical treatment (N = 25) include intralesional curettage (InC) (alone or followed by filling of the defect with bone cement), marginal excision (MEx), a wide local excision, or en bloc resection with or without reconstructive surger...

e22501Background: Treatment results of heavily pretreated refractory childhood osteosarcoma are not satisfactory. According to the data of different pilot trials progression-free survival (PFS) cur...

e11520 Background: Trastuzumab can result in sub-clinical and clinical cardiac failure manifesting as congestive heart failure (CHF), and decreased left ventricular ejection fraction (LVEF). Methods: Data was reviewed from 9837 patients in four randomized trials (NCCTG 9831, NSABP B-31, HERA, and BCIRG-06) that supported trastuzumab HER2 overexpressing adjuvant breast cancer approval. Results: Trastuzumab can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death. Herceptin can also cause asymptomatic decline in LVEF. There is a 4−6 fold increase in the incidence of symptomatic myocardial dysfunction among patients receiving trastuzumab as a single agent or in combination therapy compared with those not receiving trastuzumab. The highest absolute incidence occurs when trastuzumab is administered with an anthracycline. Clinical trials NCCTG 9831, NSABP B-31, and BCIRG-06 included arms with doxorubicin- cyclophosphamide (AC) followed by a taxane plus trastuzumab. Among 32 patients receiving adjuvant chemotherapy from studies NCCTG 9831 and NSABP B-31 who developed CHF, one patient died of cardiomyopathy and all other patients were receiving cardiac medication at last follow-up. Approximately half of the patients recovered to a normal LVEF (defined as ≥ 50%) on continuing medical management at the time of last follow-up. In BCIRG-06 the incidence of CHF was six (6) fold higher in the AC followed by docetaxel plus trastuzumab arm as compared to AC followed by docetaxel. There was a lower incidence of CHF in the non-anthracycline TCH (docetaxel, carboplatin and trastuzumab) arm in BCIRG-06 comparable to trastuzumab monotherapy. Conclusions: Cardiotoxicity manifesting as sub-clinical and clinical cardiac failure is a known side effect of trastuzumab. In an era where trastuzumab is given earlier in the treatment of breast cancer (adjuvant setting), the safety of continuation or resumption of trastuzumab in patients with trastuzumab-induced left ventricular cardiac dysfunction has not been studied. No significant financial relationships to disclose.

18190 Background: the ongoing open-label, nonrandomized clinical trial on the evaluation of the efficiency and safety of gemcitabine/cisplatin as neoadjuvant chemotherapy of operable NSCLC. Methods: 37 chemonaive patients (male- 30 (81%) and female- 7 (19%), median age 54), ECOG 0–1 with morphologically verified NSCLC recieved gemcitabine 1250 mg/m2 IV on days 1,8 plus cisplatin 75 mg/m2 IV on day 1. The follow-up period was 3 years after the surgery. Results: Most of patients recieved 3 cycles in neoadjuvant setting. IB stage had 5 (13.5%) patients, IIB- 3 (8.1%), IIIA- 23 (62.2%) and IIIB- 6 (16.2%) patients. At baseline 12 (32.3%) patients had ECOG 0 and 25 (67.7%) ECOG 1. CR was registered in 3 (8.1%) patients, PR in 12 (32.3%), SD in 19 (51.3%) and PD in 2 (5.4%) and 1 patient was not assessed. The most common hemotologic toxicity was mild/moderate neutropenia that didn’t need dose reduction or intercycle interval prolongation. 25 patients underwent curative surgery with median survival of 30 months, 1-year survival of 81%, 2-year survival- 60% and 3-year survival - 40%. There was no statistically significant dependance between the level of pathomorphosis and the intensity of clinical response.6 patients recieved explorative thoracotomy and 6 didn’t recieve any surgery. Conclusions: Preliminary results show that gemcitabine/cisplatin combination is an effective and well-tolerable neoadjuvant regimen for patients with operable NSCLC. No significant financial relationships to disclose.

13038 Background: Lenalidomide (L), CC5013, is a thalidomide (T) analog that has shown activity in multiple myeloma and myelodysplastic syndromes (MDS); including activity in pts refractory to T. Preclinical studies suggest L has more potent immunomodulatory and antiangiogenic activity than T. We have conducted a phase I clinical trial of L to determine the maximum-tolerated dose (MTD), characterize the side-effects, characterize pharmacokinetics (PK) in pts with solid tumors. Methods: Pts with refractory metastatic cancer were treated on a modified Fibonacci dose-escalation scheme with an oral daily dose of L. Therapy was continued until MTD or disease progression. Results: Forty-five pts have been enrolled (M/F: 37/8). Median age 68 yrs (range, 25–89 yrs). Tumor types include prostate cancer (36 pts), adrenal carcinoma (3 pt), renal cell carcinoma (1 pt), choleangiocarcinoma (1 pt), small intestine cancer (1 pt), colon cancer (2 pt), and melanoma (1 pt). Dose levels were: 5 mg (n = 3), 10 mg (n = 6), 15 mg (n = 3), 20 mg (n = 3 + 7), 25 mg (n = 6), 30 mg (n = 8), 35 mg (n = 6) and 40 mg (n = 3). Due to side effects the dosing schedule was modified from daily dosing to daily dosing for 21 out of 28 days. Therapy has been well tolerated with most frequent gr 1 and gr 2 toxicities include nausea (43%), myalgia (38%), pruritis/rash (54%), and fatigue (38%), neutropenia (30%) with gr 3 diarrhea (n = 1), hypotension (n = 1), pulmonary effusions (n = 1), thromboses (n = 2) and gr 4 neutropenia (n = 2), arrhythmias (n = 1), hemolysis (n = 1). Dose escalation continues. There were no differences observed between dose levels for either oral clearance values (p = 0.47) or the apparent volume of distribution (Vz) values (p = 0.23). Dose-normalized AUC(0-∞), dose-normalized peak concentrations (Cmax), or half-life (t1/2) did not vary between dose levels (p > 0.12). Conclusion: L has been well tolerated up to 35 mg/d (21 days on; 7 days off), doses higher than the recently FDA-approved doses of 5 and 10 mg/d. In this dose range L exhibits linear PK. Tolerability to myelosuppression the dose-limiting toxicity in pts with MDS may therefore be improved in pts without hematological malignancies. No significant financial relationships to disclose.