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Background NIVO is an anti-programmed cell death-1 (PD-1) monoclonal antibody; it might work even better when combined with SBRT improving clinical outcomes with a phenomenon known as abscopal effect. To date there are limited data on safety profile of combined SBRT and NIVO in mRCC. We report for the first time the toxicities occurred in phase II NIVES Study. Methods This is a phase II, single arm, multicentre study in pts with mRCC with progression disease after≤2 prior anti-angiogenic therapies and with measurable non-brain metastatic sites, at least one of which potentially suitable for SBRT. The pts included received hypofractionated radiation in one lesion at dose of 10 Gy/3 fractions after 7 days from the first infusion of NIVO. NIVO will be given as flat dose of 240 mg on day 1 every 14 days for 6 months, then switch to 480 mg q4-weekly in responding pts until PD or unacceptable toxicity. Descriptive statistics are reported for patient/tumor/treatment characteristics and observed severe Adverse Events (AEs) graded by CTCAE v. 4.03. Results Sixty-nine pts were enrolled from July 2017 to March 2019 in 11 Italian centers. 79.7% of pts had clear cell histology, median age was 67 years (range 43-85), 82.6% were male. ECOG PS was 0 in 57 pts (82.6%), only 18.8% pts had received 2 previous lines of therapy. The most frequent sites of SBRT were lung (39.4% of pts), lymphonodes (16.7%) and bone (10.6%). Toxicities of grade (G) 3-4 related to NIVO were experienced in 13 pts (18.8%); all G3-4 toxicities were outside of the irradiated area. The most frequently observed G3-4 treatment-related AEs included diarrhea (5.8%), fatigue (4.3%), anemia (2.9%) and increase of amylase/lipase (2.9%). To date no G3-4 pneumonitis were observed. Six pts (8.7%) were hospitalized due to treatment-related SAEs. Overall, 5 of 69 treated pts (7.2%) discontinued therapy because of G3-4 AEs. At the time of this analysis 32/69 pts (46%) are still on treatment. Conclusions Concurrent NIVO plus SBRT is generally well tolerated, without increased rates of common severe toxicity. Definitive data of toxicities and efficacy of the combination of immunotherapy and radiotherapy are not yet mature. Clinical trial identification NCT03469713. Legal entity responsible for the study GOIRC. Funding GOIRC. Disclosure C. Masini: Travel / Accommodation / Expenses: BMS, Janssen, Astellas, Bayer; Advisory / Consultancy: Pfizer, Novartis, Sanofi. U.F.F. De Giorgi: Research grant / Funding (institution): AstraZeneca, Roche, Sanofi; Advisory / Consultancy: Astellas, Bayer, BMS, Ipsen, Janssen, Merck, Pfizer, Sanofi; Travel / Accommodation / Expenses: BMS, Ipsen, Janssen, Pfizer. S. Buti: Advisory / Consultancy: BMS, Pfizer, MSD. M. Milella: Speaker Bureau / Expert testimony: AstraZeneca, Pfizer, EUSA Pharma. M.G. Vitale: Speaker Bureau / Expert testimony: Astellas, Ipsen, Janssen, Pierre Fabre, BMS, Pfizer, Novartis; Travel / Accommodation / Expenses: Astellas, Pfizer, Ipsen, Janssen, BMS, Novartis; Advisory / Consultancy: Janssen, BMS. G. Procopio: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer, BMS, Ipsen, MSD, Novartis, Pfizer. F. Nole: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS, Ipsen, Pfizer, Bayer, Novartis, MSD. G. Pappagallo: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen, BMS, Astellas, Janssen, Bayer, Pfizer, Novartis. C. Pinto: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche, BMS, MSD, Janssen, Pfizer, Novartis, Ipsen, Lilly, Bayer. All other authors have declared no conflicts of interest.

Background In recent years, TTs have improved the prognosis of mRCC patients (pts). Despite a not negligible number of pts received 3 TTs in clinical practice, no TTs have been evaluated as 3rd line. Aim of this study is to investigate the clinical outcome in pts who received 3 TTs. Patients and methods Pts with clear-cell mRCC who received 3 TTs were included. A questionnaire was sent to main Italian centers involved in the treatment of mRCC. Demographic data, history of RCC, type and length of first, second and third line were collected; MSKCC risk class was calculated before starting the 1st and 3rd lines, Heng class before the 3rd line. Sequences of class and specific TTs were evaluated: TKIaTKIamTOR and TKIamTORaTKI or sunitinib (SU)-sorafenib(SO)- everolimus(EV) and SU-EV-SO. Median PFS, OS and Time to Strategy Failure (TTSF: from start of 1st to end of 3rd line) were estimated with the Kaplan-Meyer method with 95% CI and curves were compared with log-rank test. The study had the ethical approval. Results 1905 pts were screened and 252 pts (13%) were treated with 3 TTs. The median age was 60 yrs (range 52–68), 73% were male, 96% underwent nephrectomy and 38% were metastatic at diagnosis. At 1st line, the Motzer class was good, intermediate, and poor in 48%, 47% and 5% of pts, respectively. PFS for type and line of therapy are reported in the table below. The TTSF was 36.4 (30.5–42.2) vs. 30.6 (26.5–34.6) mos (p = 0.11), and the OS was 52.1 (41.6–62.6) vs. 36.3 (31.2–41.4) mos (p = 0.01), for TKIaTKIam-TOR and and TKIam-TORaTKI, respectively. TTSF for SU-SO-EV was 36.5 vs. 30.4 mos for SU-EV-SO (p = 0.011). When stratified by ECOG-PS before 3rd line or baseline MSKCC, TS maintained its independent prognostic role (p = 0.002 and p = 0.004, respectively). Conclusions Only few patients received 3 lines of TTs. The sequence sunitinib-sorafenib-everolimus was associated with a better TTSF and OS as compared to the sequence sunitinib-everolimus-sorafenib. Therapy 1st line 2nd line 3rd line % PFS % PFS % PFS Sunitinib 60 10.1 31 11.2 8 14.1 Sorafenib 25 13.1 35 7.7 28 5.2 Pazopanib 2 6.4 0 / 0 / Bevac. + IFN 11 11.3 0 / 1 4.3 Everolimus 0 / 30 4.7 55 6.9 Temsirolimus 2 5.1 3 5.6 5 2.6 Other 0 / 0 / 3 3.2 TOTAL 100 11.6 100 6.8 100 6.2 Disclosure All authors have declared no conflicts of interest.

Background: Trabectedin (Yondelis®) is a minor groove DNA binding agent with suggested activity in patients with defective homologous recombinant DNA repair. This prospective phase II study was designed to evaluate activity of trabectedin in patients with BRCA mutated and BRCAness phenotype AOC (EudraCT N: 2011-001298-17). Methods: AOC patients with documented BRCA mutation or BRCAness phenotype, defined as having had at least 2 previous responses to platinum therapy, were treated with trabectedin 1.3 mg/m2 as a 3-hour i.v. infusion every 3 weeks until disease progression. According to the platinum sensitivity at the time of enrollment, patients were stratified in platinum resistant (PR, Results: A total of 100 patients were enrolled and 88 were evaluable for response (46 PR, 42 PS) after a median follow up of 6 months (range: 1.5-20). Patients had a median age of 59 years (range 49-73); most had serous-papillary histology (86%) and 60% were grade 3. Patients were pretreated with a median of 4 (range 2-14) prior chemotherapy lines and received a median of 6 (range 1-15) trabectedin cycles with a median cumulative dose of 11.0 mg/m2 (range 1.9-30). In the whole population ORR was 41%, median PFS 4.5 months, while median OS was not reached (NR). Patients with BRCA mutations (n = 7), achieved 4 PR (57.1%), 1 SD and 2 PD. Among 518 administered cycles the most frequent grade 3/4 toxicities were neutropenia 17.3%, leukopenia 7.7% and elevation of liver aminotransferases 5.2%. Evaluation of responses according to BRCA mutational status, expression profiling and DNA polymorphisms of genes involved in DNA repair is still ongoing. Conclusion: Trabectedin represents a valid treatment option in patients with platinum-sensitive AOC and documented BRCA mutation or BRCAness phenotype after multiple platinum lines. n (%) ORR CR PR SD DCR (ORR +SD PD Median PFS (months) Median OS (months) PR n = 46 (%) 15 (32.6) 0 15 (32.6) 12 (26.1) 27 (58.7%) 19 (41.3) 2.7 10 PS n = 42 (%) 21 (50) 4 (9.5) 17 (40.5) 10 (23.8) 31 (73.8%) 11 (26.2) 6 NR ORR, overall response rate; CR, complete response; PR, partial response; SD, stabilization of disease; DRC, disease control rate; PD, progression of disease; PFS, progression-free survival; OS, overall survival; NR, not reached. Disclosure: C. Rigamonti: I am an employee of PharmaMar, S.A (Grupo Zeltia). All other authors have declared no conflicts of interest.

Methods: Data from 19 Italian centers involved in the treatment of metastatic RCC were retrospectively collected. Kaplan-Meier and log-rank test methods were used to evaluate the overall survival (OS). Clinical variables considered were sex, age, concomitant metastasis to other sites, surgical resection of PM-RCC and time to PM-RCC occurrence. A subsequent univariate and backward multivariate Cox regression model was fitted to the data to correct for the effect of covariates. Results: 103 patients were enrolled in the analysis; 66 of them were males. Median age was 67 yrs (range 43–85 yrs). PM-RCC were synchronous in only 3 patients (3%). In 56 patients (54%), the pancreas was the only metastatic site, whereas in the other 47 patients lung (57%), lymph nodes (28%) and liver (21%) were the most common concomitant metastatic sites. Median time for PM-RCC occurrence was 9.6 yrs (range 0–24 yrs) after nephrectomy. Surgical resection of PM-RCC was performed in 40 patients (39%) and consisted of total (21%), distal (71%) or central pancreatectomy (8%). Median OS was not reached in patients who underwent surgical resection of PM-RCC and 11.1 yrs in the unresected patients (p Conclusions: The presence of PM-RCC is associated with long survival, which is surprisingly not associated with surgical resection, time of PM-RCC occurrence and the presence of concomitant metastases to other sites, although these data should be confirmed in a larger population. Disclosure: All authors have declared no conflicts of interest.

Background Study results demonstrated that IFN augments BEV activity and improves median PFS in pts with mRCC. Thus, combination BEV + IFN is a standard first-line treatment option for mRCC. Combining BEV with the mTOR inhibitor EVE may be an efficacious and well-tolerated treatment option. The open-label, phase II RECORD-2 trial compared first-line EVE + BEV and IFN + BEV in mRCC. Patients and methods: Therapy-naive pts with clear cell mRCC and prior nephrectomy were randomized 1:1 to BEV 10 mg/kg IV every 2 weeks with either EVE 10 mg oral daily or IFN (9 MIU SC 3 times/week, if tolerated). Tumour assessments were every 12 weeks. Primary objective was treatment effect on progression-free survival (PFS) per central review based on an estimate of the chance of a subsequent phase III trial success (50% threshold for phase II success). Results In EVE + BEV (n = 182) and IFN + BEV (n = 183) arms, median age was 60/60 years, 76/72% of pts were men, MSKCC risk was favourable/intermediate/poor in 36/57/7% and 36/57/7% of pts, and 43/46% of pts had >2 organs involved, respectively. For EVE + BEV and IFN + BEV, median treatment duration was 8.5/8.3 months, respectively; 23/26% of pts discontinued due to AEs. In EVE + BEV and IFN + BEV arms, median PFS by central review was 9.3/10.0 months (HRIFN/EVE, 0.91; 95% CI, 0.69-1.19; P =0.485), respectively; probability of subsequent phase III success was 5.1%. Results of central and local PFS analysis were consistent. Objective response rate was 27/28% in EVE + BEV and IFN + BEV arms, respectively. Median overall survival (OS) was not reached in the EVE + BEV arm and was 25.9 months (95% CI: 21.1, 30.2) in the IFN + BEV arm. Most frequent AEs (%) were stomatitis (63), proteinuria (49), diarrhoea (39), hypertension (38), and epistaxis (35) in EVE + BEV arm and decreased appetite (45), fatigue (41), proteinuria (37), and pyrexia (35) in IFN + BEV arm. Conclusions In RECORD-2, PFS and tolerability were similar for first-line EVE + BEV and IFN + BEV. Final OS analysis will occur after 2-year follow-up. Disclosure A. Ravaud: Alain Ravaud is a member of global, European, and/or French boards on urological tumors for Pfizer, Novartis, GlaxoSmithKline, Bayer-Schering, and Dendreon, and has received institutional grant support from Pfizer, Novartis, and Roche. O. Anak: Ozlem Anak is an employee of Novartis Pharma AG. D. Pelov: Diana Pelov is an employee of Novartis Pharmaceuticals Corporation. A. Louveau: Anne-Laure Louveau is an employee of Novartis Pharma S.A.S. T. M-H: Tay M-H is a speaker for an advisory board for Novartis Pharmaceuticals Corporation. B. Melichar: Bohuslav Melichar has received honoraria from Novartis and Roche and served on an advisory board for Roche. All other authors have declared no conflicts of interest.

Background On the basis of a few published data, sunitinib and sorafenib can be administered safely to patients (pts) with metastatic renal cell carcinoma (mRCC) and end-stage renal disease on haemodialysis (HD). Aim of this study was to investigate the safety and efficacy of temsirolimus and everolimus in pts with mRCC on HD. Patients and methods between September 2007 and February 2012, 13 pts with mRCC undergoing HD were treated with temsirolimus and everolimus in 6 Italian Institutions. We retrospectively reviewed the medical records of these pts to evaluate the doses of mTOR inihibitors administered, the tolerability and the activity of the treatment. Results Gender: 9 males/4 females; median age: 63 years (range 47–79). All pts were undergoing HD, in 7 cases for bilateral nephrectomy; the time interval between the start of HD and the start of mTOR inhibitors treatment was 37 months. Everolimus was administered at 10 mg daily in 5 pts and at 5 mg in one patient; 7 pts received temsirolimus at 25 mg weekly. Everolimus was administered as second-line treatment in 4 pts, as third and fourth-line in two pts; temsirolimus was given as first-line treatment to 4 pts, as second-line to one patient and as third-line to 2 pts. No unexpected adverse event (AE) and no grade 4 haematological or non-haematological toxicity were reported. The most common grade 1–2 non-haematological treatment-related AEs were fatigue (9/13 pts), dyslipidemia (4/13 pts), oral mucositis in 2/13 pts. A grade 3 dyspnea due to interstitial pneumonia led to treatment discontinuation. The most frequent grade 1–2 haematologic toxicity was anemia (10/13 pts). None of the patients had to change the number of dialysis sessions during mTOR inhibitors treatment. None of the pts experienced an objective response while a disease stabilization was observed in 7 pts. At the time of the analysis, 7 pts had died due to disease progression. The estimated median progression-free survival (PFS) of this cohort of pts was 6.1 months. Conclusions In this small retrospective series of pts the incidence of AEs was as expected, and a prolonged PFS was observed. The use of temsirolimus and everolimus is not contraindicated in pts with mRCC and severe renal impairment on HD. Disclosure All authors have declared no conflicts of interest.