anyone has data on pertuzumab+trastuzumab v.s pert+tras+docetaxol

[Nguyen]

Hello,

Does anyone have information on the combination "trastuzumab and pertuzumab" vs "trastuzumab + Pertuzumab + Docetaxol"?

Any efficacy data on "trastuzumab + Pertuzumab" without docetaxol are also appreciated.

Many Thanks,

Nguyen

[schoonder]

Roche's Dec 3 presentation slides 28 - 32 show some comparison data on PFS.

http://www.roche.com/investors/ir_agenda.htm?tab=2

[Nguyen]

From below abstracts: "...Pertuzumab and trastuzumab without chemotherapy eradicated tumours in a proportion of women and showed a favourable safety profile...". But efficacy is much higher with docetaxol.

Nguyen

Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial.

Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P,Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P.
Source
Oncologia Medica, San Raffaele Cancer Centre, Milan, Italy. gianni.luca@hsr.it
Abstract
BACKGROUND:
Studies with pertuzumab, a novel anti-HER2 antibody, show improved efficacy when combined with the established HER2-directed antibody trastuzumab in breast cancer therapy. We investigated the combination of pertuzumab or trastuzumab, or both, with docetaxel and the combination of pertuzumab and trastuzumab without chemotherapy in the neoadjuvant setting.
METHODS:
In this multicentre, open-label, phase 2 study, treatment-naive women with HER2-positive breast cancer were randomly assigned (1:1:1:1) centrally and stratified by operable, locally advanced, and inflammatory breast cancer, and by hormone receptor expression to receive four neoadjuvant cycles of: trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) plus docetaxel (75 mg/m(2), escalating, if tolerated, to 100 mg/m(2) every 3 weeks; group A) or pertuzumab (loading dose 840 mg, followed by 420 mg every 3 weeks) and trastuzumab plus docetaxel (group B) or pertuzumab and trastuzumab (group C) or pertuzumab plus docetaxel (group D). The primary endpoint, examined in the intention-to-treat population, was pathological complete response in the breast. Neither patients nor investigators were masked to treatment. This study is registered with ClinicalTrials.gov, number NCT00545688.
FINDINGS:
Of 417 eligible patients, 107 were randomly assigned to group A, 107 to group B, 107 to group C, and 96 to group D. Patients given pertuzumab and trastuzumab plus docetaxel (group B) had a significantly improved pathological complete response rate (49 of 107 patients; 45•8% [95% CI 36•1-55•7]) compared with those given trastuzumab plus docetaxel (group A; 31 of 107; 29•0% [20•6-38•5]; p=0•0141). 23 of 96 (24•0% [15•8-33•7]) women given pertuzumab plus docetaxel (group D) had a pathological complete response, as did 18 of 107 (16•8% [10•3-25•3]) given pertuzumab and trastuzumab (group C). The most common adverse events of grade 3 or higher were neutropenia (61 of 107 women in group A, 48 of 107 in group B, one of 108 in group C, and 52 of 94 in group D), febrile neutropenia (eight, nine, none, and seven, respectively), and leucopenia (13, five, none, and seven, respectively). The number of serious adverse events was similar in groups A, B, and D (15-20 serious adverse events per group in 10-17% of patients) but lower in group C (four serious adverse events in 4% of patients).
INTERPRETATION:
Patients given pertuzumab and trastuzumab plus docetaxel (group B) had a significantly improved pathological complete response rate compared with those given trastuzumab plus docetaxel, without substantial differences in tolerability. Pertuzumab and trastuzumab without chemotherapy eradicated tumours in a proportion of women and showed a favourable safety profile. These findings justify further exploration in adjuvant trials and support the neoadjuvant approach for accelerating drug assessment in early breast cancer.

['lizbeth]

Perjeta is listed on Roche's pipeline as filing post 2014 for second line MBC. Perjeta is to be filed for early breast cancer in 2016. TDM1 filed as first line MBC 2014.

http://www.roche.com/research_and_development/pipeline/roche_pharma_pipeline.htm

I have heard different information on FDA approvals that are expected. I can only guess these will be early approvals or fast track?