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Background Monthly Denosumab (DN) has shown superiority over zoledronic acid (ZA) in delaying skeletal related events. Randomized trials have shown that ZA given every 12 weeks (q12w) is non-inferior to ZA given every 4 weeks (q4w). The primary endpoint of the REDUSE-trial is non-inferiority for SSE for DN q12w versus q4w. Here we present early data for hypocalcemia (HC), a secondary endpoint. Methods Patients with bone metastasis from breast cancer (BC) not pretreated with DN or Bisphosphonates were randomized 1:1 to receive DN q4w (Arm A) versus q12w (Arm B) after a 3-month induction phase with q4w therapy for both arms. All patients received vitamin D 400 U (VitD) and calcium (Ca) 500 mg daily. Measurement of albumin-corrected serum-Ca was mandatory before each DN injection (HC defined as Results 351 BC-patients are currently included (177 in Arm A, 174 in Arm B). HC was the most common side effect with a rate of 20% in the first 16 weeks (during the induction phase with DN q4w for both Arms) and 19% afterwards (combined for Arms A and B). After week 16 HC-prevalence differed between the two arms: while HC was present in 25% in Arm A (q4w), the rate was only 12% in Arm B (q12w). Grade 3 HC (i.e. corrected Ca 1.5 - 1.74 mmol/l or hospitalisation indicated) was rare (0.3%), no grade 4 HC occurred. After 1 year of treatment, the rate of HC compared to the induction phase had decreased in Arm B but not in Arm A (A: 25%, B: 12%). Since HC improved in more patients in Arm B than in Arm A whereas it worsened in more patients in Arm A than in Arm B, a remarkable difference for HC resulted between the two arms. Rates of hypocalcemia and change of severity after week 16* Arm A (N = 177)Arm B (N = 174)Rates of hypocalcemian (%)n (%)Patients with hypocalcemia at any time49 (28%)46 (26%)Patients with hypocalcemia after week 16*44 (25%)21 (12%) Change in hypocalcemia grade after week 16*for the 49 patients with hypocalcemiafor the 46 patients with hypocalcemiaWorsening25 (51%)8 (17%)Stable10 (20%)9 (20%)Improving14 (29%)29 (63%) *week 16: i.e. the time where the schedules of DN begin to differ between Arm A and Arm BArm A: DN q4w for weeks 1 - 12 and likewise thereafter / Arm B: DN q4w for weeks 1 - 12 and q12w thereafter Conclusions In our trial up to 20% of all BC patients treated with DN experienced HC in the q4w induction phase despite mandatory supplementation of VitD and Ca. This rate is considerably higher than the numbers reported in the registration trials of DN (where it was 5.5% for BC). After the induction phase, HC is markedly reduced in the q12w arm compared to q4w. This suggests that DN given q12w has a more favorable long-term safety profile in terms of HC compared to DN q4w. Citation Format: Müller A, Templeton AJ, Hayoz S, Hawle H, Hasler-Strub U, Schwitter M, Pestalozzi BC, Pagani O, Bützberger P, Wehrhahn T, Rauch D, Inauen R, Betticher D, Zaman K, Bodmer A, Popescu RA, Rothschild S, Schardt J, Borner M, Fuhrer A, Schär C, Gillessen S, von Moos R, For the Swiss Group for Clinical Cancer Research (SAKK). Incidence of hypocalcemia in patients with metastatic breast cancer under treatment with denosumab: A non-inferiority phase III trial assessing prevention of symptomatic skeletal events (SSE) with denosumab administered every 4 weeks versus every 12 weeks: SAKK 96/12 (REDUSE) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-18-01.

Patients with plasma cell myeloma may initially present to their dentists or dental surgeons with toothache, loose teeth, or gingival masses. An X-ray of the jaw can reveal osteolyses. In addition, accumulation of monoclonal light chains in AL-amyloidosis can lead to macroglossia. It is prudent that the dentist or dental surgeon recognizes the underlying disease and refers the patient to the oncologist or hematologist for further workup to prevent the complications of plasma cell myeloma such as renal impairment, fractures, bone pain, infections, hypercalcemia, anemia, or heart failure. Another area where the dentist or dental surgeon is involved with patients suffering from plasma cell myeloma is prevention and therapy of osteonecrosis of the jaw, occurring after administration of bisphosphonates or denosumab for osteolytic bone disease. The case report presented here shows a patient complaining of toothache for whom recognition of a systemic disease by the dentist led to the diagnosis of plasma cell myeloma, highlighting the need for interdisciplinary cooperation. As recent years have seen many changes in the management of patients with plasma cell myeloma, an update for dentists and dental surgeons is warranted.

BACKGROUND: The majority of germ cell tumour (GCT) patients can be cured by orchiectomy followed by active surveillance or subsequent systemic and/or local treatments. There are various guidelines for a structured follow-up including radiographic and clinical examinations.OBJECTIVE: The Swiss Austrian German Testicular Cancer Cohort Study (SAG TCCS) prospectively evaluates follow-up, indicator of relapse and late toxicities. This is a descriptive analysis; we present baseline characteristics and treatment strategies for the first 299 patients with primary GCT or relapsed GCT after completion of treatment.RESULTS: Of the patients included in this study, 192 (64.2%) had seminoma and 107 (35.8%) non-seminoma. Mean age was 41 years (standard deviation [SD] 11.7) for seminoma and 31 (SD 9.3) years for non-seminoma patients. Median tumour size was 3.5 cm (interquartile range 2.5¬‒5.0 and 2.3‒4.5 in seminoma and non-seminoma, respectively) in both histological groups. Among seminoma patients, 81 (42.2%) had primary tumours >4cm; 154 (80.2%) seminoma patients had stage I, 26 (13.5%) stage II and 12 (6.3%) stage III disease. Fifty-seven (53.3%) non-seminoma tumours were stage I, 29 (27.1%) stage II and 21 (19.6%) stage III. Marker-positive disease was present in 58 (30.2%) seminoma patients and 78 (72.9%) non-seminoma patients. Of 154 stage I seminoma patients, 89 (57.8%) chose active surveillance and 65 (42.2%) adjuvant chemotherapy. Twenty-six (45.6%) stage I non-seminoma patients had high-risk disease; 23 of these were treated with adjuvant chemotherapy and 3 chose active surveillance. Among the 30 (52.6%) low risk stage I patients, all opted for active surveillance. Twelve (46.2%) stage II seminoma patients had radiotherapy, 14 (53.8%) were treated with three to four cycles of chemotherapy. All stage III seminoma patients, and all stage II and III non-seminoma patients were treated with three to four cycles of chemotherapy. Treatment decisions were made at the respective centre. Eleven patients did not receive therapy that conformed with guidelines.CONCLUSION: It is important to enrol GCT patients in prospective studies in general, but also in follow-up studies to assess baseline characteristics, oncological outcome, and long-term toxicity and to validate the performance of follow-up schedules. This is the first time that the distribution of disease, detailed baseline characteristics and the respective treatment of men with GCT is collected in a prospective manner in German speaking countries (Switzerland, Austria and Germany) and therefore patterns of care have been evaluated. SAG TCCS results will inform on future modifications of surveillance schedules and follow-up procedures.TRIAL REGISTRATION NUMBER: NCT02229916 (Clinicaltrials.gov).

139 Background: DN given q4w has shown superiority in delaying skeletal related events over q4w zoledronic acid (ZA). Recently it has been demonstrated that ZA q12w is non-inferior to ZA q4w. The objective of REDUSE is to show non-inferiority for DN q12w versus q4w in terms of SSE. Here we present an interim analysis for the secondary endpoint HC. Methods: Patients (pts) with castration resistant prostate cancer (planned N=690) were randomized 1:1 to DN q4w (Arm A) vs q12w (Arm B) after a 16 week induction phase with application q4w. All pts received vitamin D (ViD) 400 U and calcium (Ca) 500 mg daily. Measurement of corrected serum-Ca was mandatory before each DN injection. This interim analysis was performed after 3.5 years of accrual. Men who received ≥ 1 dose of DN were considered evaluable. Results: 383 pts were evaluable. HC occurred in 28.7% during the first 16 weeks (DN q4w for all pts) and 30.2% afterwards. After the induction phase HC occurred in 40.2% in Arm A and in 20.3% in Arm B. Grade 3 (2.1%) and 4 (1.1%) HC were rare, most frequently occurring in the first 16 weeks. After 1 year of treatment, the incidence of HC was lower in both arms (A: 30.8%, B: 18.7%). A clinically relevant difference for HC was noted between the two arms after the induction phase (table). Conclusions: In our trial nearly 30% of all men treated with DN experienced HC in the q4w induction phase despite mandatory supplementation of calcium and ViD and measurement of Ca. This rate was considerably higher than reported in the registration trials of DN (13%). After induction treatment the incidence of HC is considerably lower in the q12w arm compared to q4w. This suggests that DN given q12w has a more favorable long time toxicity profile (HC) compared to DN q4w. Change in HC grade after week 16 (week 1 – 12: DN q4w Arm A+B), thereafter q4w in Arm A and q12w in Arm B. Clinical trial information: NCT02051218. [Table: see text]

TPS5086Background: The current first-line treatment for patients with CRPC and disease progression is either treatment with abiraterone acetate/prednisone, ENZ, or treatment with docetaxel in more ...