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Other Cancers . . .

AIOM post ASCO Review: updates and news from the Annual Meeting in Chicago. Other Cancers . . . Genito-Urinary Track. Sergio Bracarda U.O.C. di Oncologia Medica Dipartimento di Oncologia Ospedale San Donato USL8, Arezzo . Bologna, 19-20 Giugno 2010. Loc. Av P. Ca.

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Other Cancers . . .

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  1. AIOM post ASCO Review: updates and news from the Annual Meeting in Chicago Other Cancers . . . Genito-Urinary Track Sergio Bracarda U.O.C. di Oncologia Medica Dipartimento di Oncologia Ospedale San Donato USL8, Arezzo Bologna, 19-20 Giugno 2010

  2. Loc. Av P. Ca

  3. Impact of RT combined with androgen deprivation (ADT) versus ADT alone for local control in clinically Loc.Av prostate cancer. N. Mottet. Abs: 4505, - Study Population: T3- 4, or pT3 N0M0 (93% T3 disease) (130 vs 133 pts) - ADT (3 yr LHRH) vs ADT combined with RT (70 ± 4 Gy over 7 wks). ADT+RT ADT mean baseline PSA: 52 42 (p = 0.79). Gleason Score: 48% 54% 5 yr PFS: 60,9% 8,5% (p< 0,001). -yr Clinical PFS: 88.7% 62.3% (p< 0.001). 5-yr incidence of local PD: 9.7% 29.0% (p< 0.0002) 5-yr incidence of met. PD: 3.0% 10.8% (p< 0.018) 5.Yr OS no diff. 5-yr specific OS: 93.2% 86.1% Conclusions: ADT+RT significantly reduces risk of clinical PD (mainly due to locoRegional control. Combined Tx should be the standard approach for pts with a significant life expect.

  4. Intergroup randomized phase III study of ADT plus RT in loc.Av P Ca. (NCIC-CTG, SWOG, MRC-UK, INT: T94-0110; NCT00002633). P.R. Warde, Abs: CRA4504 To assess the effect of RT on OS when added to lifelong ADT in LocAv CaP. T3/T4 or T2, PSA >40 µg/l or T2 PSA >20 µg/l and Gls ≥ 8 (25) and N0 /NX, M0 (1057) (119) Lifelong ADT ±RT (65-69 Gy to prostate ±SV ± 45Gy to pelvic LFN). 1205 pts randomized from 1995 to 2005, 602± to ADT and 603 to ADT+RT 7-yr OS: 74 vs 66%. HR 0.77, 95% CI 0.61-0.98, p=0.033). 7-yr DSS: 90 vs 79%. HR 0.57 (95% CI 0.41-0.81, p=0.001) favoring ADT+RT 10 yr cumulative disease specific death rates: 15% (ADT+RT) vs 23% Grade ≥2 late GI toxicity rates similar in both arms OS and DSS benefit for the combined modality approach (ADT+RT) Combined ADT+RT should be the standard treatment approach for these pts.

  5. A randomized phase III trial of denosumab versus zoledronic acid in pts with bone metastases from CRPC. K. Fizazi Abs: LBA4507 Background: Bone metastases from CRPC are associated with RANKL-mediated osteoclast activation resulting in bone destruction and skeletal-related events (SRE). Ph. III, randomized, double-blind, active-controlled trial compared the efficacy and safety of denosumab vs. zoledronic acid (ZA) in patients with metastatic CRPC. Primary endpoint: time to first on-study SRE 1901 Pts with CRPC and at least 1 bone met (no prior IV bisphosphonate), received either SC denosumab 120 mg and IV placebo (n = 950), or SC placebo and IV ZA 4 mg (n = 951) Median time to first on-study SRE: 20.7m denosumab vs. 17.1m ZA (+3.6 m). (HR 0.82 ; 95% CI: 0.71, 0.95 ; p = 0.008.) Denosumab also significantly delay the time to first and subsequent on-study SRE (multiple event analysis) (HR 0.82 ; 95% CI: 0.71, 0.94 ; p = 0.004).

  6. A randomized phase III trial of denosumab versus zoledronic acid in pts with bone metastases from CRPC. K. Fizazi Abs: LBA4507 - Overall AE rates (97% each) • serious AEs (63% denosumab, 60% ZA) were similar, denosumab ZA - AEs of hypocalcemia were reported in 12.3% 5.4% - Osteonecrosis of the jaw occurred in: Year 1 1.1% 0.5% Year 2 2.3% 0.8% (p = 0.09). OS (HR 1.03 ; 95% CI: 0.91, 1.17 ; p = 0.65) and TTP (HR 1.06; 95% CI: 0.95, 1.18; p = 0.30) were similar between tx arms.

  7. mCRPC

  8. Docetaxel (D) plus high-dose Calcitriol versus D plus prednisone (P) for Pts with progressive CRPC: Results from the phase III ASCENT2 trial. H.I. Scher. Abs: 4509 A placebo-controlled ph. II study in progressive CRPC pts suggested a potentially increased OS by combining DCT with HD calcitriol (DN-101) vs DCT alone. ASCENT-2: 953 men with CRPC. Primary endpoint: OS - ASCENT arm (45 µg DN-101, 36 mg/m2 DCT, 24 mg DEX wk for 3/4 weeks) - Control arm (5 mg PDN bid, and 75 mg/m2 DCT and 24 mg DEX q21). Median OS: ASCENT, 16.8 m (95% CI, 15.8-19.3) Control, 19.9 m (95% CI, 18.6-22.7) Multivariate analysis ASCENT associated with shorter os (HR=1.33; p=0.019). Difference may be due to weekly DCT dosing in the ASCENT arm, inferior to DCT q21 in the TAX 327 trial (NEJM 351:1502, 2004). Deaths in each study arm ASCENT n=477 Control n=476 Disease-specific 142 (29.8%) 108 (22.7%) Other cause 32 ( 6.7%) 30 ( 6.3%)

  9. A randomized, double-blind, placebo-controlled ph. III trial comparing Docetaxel, Pdn, and Placebo with Docetaxel, Pdn, and Bevacizumab in mCRPC: Survival results of CALGB 90401. W. K. Kelly, Abs: LBA4511 VEGF blockade suggested as an appropriate potential strategy in mCRPC. R Ph. III study in 1050 pts with mCRPC. Primary endpoint OS DCT (75 mg/m2 IV q 21 days), plus Pdn (5 mg po BID) with Bevacizumab (15 mg/kg given iv q21 following DCT) or placebo. (dex 8 mg os 12, 3, 1h prior to DCT)

  10. A randomized, double-blind, placebo-controlled ph. III trial comparing Docetaxel, Pdn, and Placebo with Docetaxel, Pdn, and Bevacizumab in mCRPC: Survival results of CALGB 90401. W. K. Kelly, Abs: LBA4511 Conclusions: Despite an improvement in PFS, measurable disease ORR and PSA response, adding bevacizumab to DCTdid not improve OS in CRPC.

  11. Cabazitaxel or Mitoxantrone with pdn in pts with mCRPC previously treated with docetaxel: Final results of a multi national ph. III trial (TROPIC). J.S. De Bono. Abs: 4508^ Treatment of mCRPC following DCT failure due to PD or toxicity is an unmet medical need. TROPIC Trial: 755 Men with mCRPC on PD after a DCT (cumulative dose ≥225 mg/m2). Primary endpoint OS. ITT analysis 10 mg/day of pdn with Mitoxantrone 12 mg/m2 (MP) 10 mg/day of pdn with Cbz 25 mg/m2 (CbzP), both administered q21. Mitox/Pdn Caba/Pdn Measurable 54.1% 53.2% Visceral 24.9% 24.9% Median n° of Cycles 4 (1-10) 6 (1-10) Median PFS (ITT) 1.4m 2.8m Median OS (ITT) 12.7m 15.1m (+2.4m) ORR 4.4% 14.4%

  12. CbzP vs. MP Cabazitaxel or Mitoxantrone with pdn in pts with mCRPC previously treated with docetaxel: Final results of a multi national ph. III trial (TROPIC). J.S. De Bono. Abs: 4508^

  13. Cabazitaxel or mitoxantrone with pdn in pts with mCRPC previously treated with docetaxel: Final results of a multi national ph. III trial (TROPIC). J.S. De Bono. Abs: 4508^ CbzP group had a statistically significantly longer Overeall Survival compared with MP (p<0.0001). Most frequent Gr 3/4 toxicity was neutropenia (81.7% CbzP; 58.0% MP); rates of febrile neutropenia were 7.5% and 1.3%, respectively. Safety Mitox/Pdn Caba/Pdn Neutropenis sepsis 1.3% 7.5% Diarrhoea (gr ≥3) 0.3% 6.2% Toxic deaths 1.9% 4.9% Conclusions: Men with mCRPC progressing after DCT benefit from CbzP with longer OS, TTP (by tumor assessments and PSA) and higher ORR.

  14. mRCC

  15. The high-dose aldesleukin (HD IL-2) "SELECT" trial in pts with mRCC. D. F. McDermott. Abs: 4514 • Background: HD IL-2 produced a 14% CR+PR rate and durable remissions in phase II trials. The Cytokine Working Group conducted the present trial to identify pts likely to respond to Rx improving the therapeutic index of HD IL-2. • Pathology risk classification, CAIX staining and creation of a tissue microarray. • Results: 120 eligible pts enrolled between November 2007 and July 2009. 72% = ECOG PS 0, 71% = MSKCC risk, (good 26% / int 69% / poor 5%) 96% = clear cell RCC 99% = prior nephrectomy. • Investigator assessed RR = 29% (35/120) (7 CR, 28 PR) • median PFS: 4.4 m with 20 responses ongoing (range 4-35+ mo). • Median response duration: 23.3m • Durable responses: 17 (42%) • RR for pts with clear cell RCC = 30% (35/115) (95% CI = 22%-40%, p=0.0004). NO Responses in non-clear RCC (5 pts). Two treatment-related deaths.

  16. Can the combination of Temsirolimus and Bevacizumab improve the treatment of mRCC? Results of the randomized TORAVA phase II trial. B.J. Escudier. Abs: 4516 Untreated mRCC pts randomized in a 2:1:1 ratio. Primary objective was the non-progression rate at 48 weeks (NPR-48) for arm A. 171 pts randomized: 88 (51%), 42 (25%) and 41 (24%) to arms A, B and C 80 T-B combination (arm A), 40 Sunitinib (arm B) 40 Bevacizumab and a-IFN (arm C) Treatments prematurely stopped for other reasons than PD in 43% (A), 12% (B) and 23% (C). Grade 3/4 events were observed in 36%, 14% and 27% pts in arms A, B, C respectively; two toxic deaths occurred in arm A. NPRs-48 were: ORR PFS 43.2% (95% CI, 32.7-54.2), 25% 8.2m 47.6% (95% CI, 32.0-63.6) 24% 8.2m 65.9% (95% CI, 49.4-79.9) 34% 16.8m

  17. TCC

  18. Randomized phase III trial comparing adjuvant pct/gem/ cisplatin (PGC) to observation in resected invasive bladder cancer: Results of the Spanish Oncology GU Group (SOGUG) 99/01 study. L.G. Paz-Ares, Abs: LBA4518 Approximately half of pts with resected invasive bladder cancer will die within the first 3 years after surgery due to disease relapse, mainly systemic. Eligibility criteria: pT3-4 and/or pN+. Primary objective; overall survival (OS). Eligible pts assigned to: observation or 4 cy of PGC (PCT 80 mg/m2 d1,8, Gem 1gr/m2 d1,8 and DDP 70 mg/m2 d1) q21. Results: study open in July 2000 and prematurely closed due to poor recruitment in July 2007, with 142 patients randomized (74 to observation and to 68 to PGC treatment). OS (ITT population) significantly prolonged in PCG arm (median NR; 5yr OS: 60%) compared to observation (median 26m; 5yr OS: 31%) (p<0.0009). DFS (p<0.0001), TTP (p<0.0001) and disease specific survival (p<0.0002) were also superior in the PGC arm. Does adjuvant PGC improves OS and DFS following cystectomy in high risk invasive bladder cancer?

  19. ASCO 2010: G.U. Conclusions • Loc.Av P.Ca: RT+ADT, standard approach • CRPC: DCT+Pdn remain standard approach • Denosumab: need of more data ? • 2° Line mCRPC: Cabazitaxel effective, but which dosage in daily activity ? • mRCC: ImmunoTherapy come back again ? • Adj. CT in TCC: actual contradictory & insufficient data

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