FIRSTANA Trial - Cabazitaxel 20/25 mg v. Docetaxel 75 mg

[pjoshea13]

New study below [1]. MedScape piece [2].

{Note: doses are per meter squared. Too bad text is changed during pasting to "/m2")

"C20 and C25 did not demonstrate superiority for {overall survival} versus D75 in patients with chemotherapy-naïve mCRPC. Tumor response was numerically higher with C25 versus D75; pain PFS was numerically improved with D75 versus C25. Cabazitaxel and docetaxel demonstrated different toxicity profiles, with overall less toxicity with C20."

So choose your poison? Do you want less toxicity, less pain or greater tumor response?

"Median {progression-free survival} was 4.4 months with C20, 5.1 months with C25, and 5.3 months with D75".

"Estimated median {overall survival} rates were very similar in each of the three treatment groups, at 24.5 months for men in the C20 arm; 25.2 months for those in the C25 arm, and 24.3 months for those in the D75 arm." [2] <Estimated!>

"Men receiving cabazitaxel were more likely to experience febrile neutropenia, neutropenic infection, diarrhea, and hematuria than those who received docetaxel."

"In contrast, men treated with docetaxel were more likely to experience peripheral neuropathy, stomatitis, peripheral edema, alopecia, and nail disorders than those who received cabazitaxel."

"Median" stats convey little about the experience of the 50% who do better. How many do much better than two years? Are the bell curves similar? & so on.

-Patrick

[1] ascopubs.org/doi/abs/10.120...

Stéphane Oudard, Karim Fizazi, Lisa Sengeløv, Gedske Daugaard, Fred Saad, Steinbjørn Hansen, ...

Abstract

Purpose

In patients with metastatic castration-resistant prostate cancer (mCRPC), overall survival (OS) is significantly improved with cabazitaxel versus mitoxantrone after prior docetaxel treatment. FIRSTANA (ClinicalTrials.gov identifier: NCT01308567) assessed whether cabazitaxel 20 mg/m2 (C20) or 25 mg/m2 (C25) is superior to docetaxel 75 mg/m2 (D75) in terms of OS in patients with chemotherapy-naïve mCRPC.

Patients and Methods

Patients with mCRPC and Eastern Cooperative Oncology Group performance status of 0 to 2 were randomly assigned 1:1:1 to receive C20, C25, or D75 intravenously every 3 weeks plus daily prednisone. The primary end point was OS. Secondary end points included safety; progression-free survival (PFS); tumor, prostate-specific antigen, and pain response; pharmacokinetics; and health-related quality of life.

Results

Between May 2011 and April 2013, 1,168 patients were randomly assigned. Baseline characteristics were similar across cohorts. Median OS was 24.5 months with C20, 25.2 months with C25, and 24.3 months with D75. Hazard ratio for C20 versus D75 was 1.01 (95% CI, 0.85 to 1.20; P = .997), and hazard ratio for C25 versus D75 was 0.97 (95% CI, 0.82 to 1.16; P = .757). Median PFS was 4.4 months with C20, 5.1 months with C25, and 5.3 months with D75, with no significant differences between treatment arms. Radiographic tumor responses were numerically higher for C25 (41.6%) versus D75 (30.9%; nominal P = .037, without multiplicity test adjustment). Rates of grade 3 or 4 treatment-emergent adverse events were 41.2%, 60.1%, and 46.0% for C20, C25, and D75, respectively. Febrile neutropenia, diarrhea, and hematuria were more frequent with C25; peripheral neuropathy, peripheral edema, alopecia, and nail disorders were more frequent with D75.

Conclusion

C20 and C25 did not demonstrate superiority for OS versus D75 in patients with chemotherapy-naïve mCRPC. Tumor response was numerically higher with C25 versus D75; pain PFS was numerically improved with D75 versus C25. Cabazitaxel and docetaxel demonstrated different toxicity profiles, with overall less toxicity with C20.

[2] medscape.com/viewarticle/88... &

medscape.com/viewarticle/88... (page 2)

[Hidden]

It is a case of "pick your poison" literally. Cabzitexel is better as a second-line chemo treatment. Most MOs will try Taxotere first. Cabizitaxel often works when there is resistance to Docetaxel.

The toxicity profiles are different but roughly the same in terms in overall toxicity. I spoke with one of my oncologists yesterday and she thinks Cabazitaxel gets more of a bad rap because by the time people go on it "they are already pretty beat up from chemo".

[Hidden]

Here's more on the subject

ascopost.com/News/23626

[pjoshea13 in reply to Hidden]

Gregg,

Perhaps both together, at lower doses, would have synergy & be more effective? Rather than one after the other.

-Patrick

[Hidden in reply to pjoshea13]

Interesting thought. I wonder if anyone has tried that.

[BigRich]

Thank you Patrick; you continue to increase my knowledge database.

Rich