First and second-line chemotherapy - OncologyPRO...FIRST AND SECOND-LINE CHEMOTHERAPY Session 5...
Transcript of First and second-line chemotherapy - OncologyPRO...FIRST AND SECOND-LINE CHEMOTHERAPY Session 5...
FIRST AND SECOND-LINE CHEMOTHERAPY
Session 5
Chemotherapy for castration refractory prostate cancer
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• high disease burden including those with visceral metastases, ≥4 bone metastases including ≥1 bone lesion beyond the vertebral column
• volume of bone metastases was measured by number of lesions and location (axial or appendicular skeleton) and not by stringent volume criteria, given the difficulties of measuring tumor volume in bone.
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Therapies in Addition to Androgen-Deprivation Therapy:Therapies with demonstrated survival and quality-of-life benefits:● Docetaxel and prednisone should be offered• Benefit: moderate; • harm: moderate; • evidence strength: strong; • recommendation strength:
moderateTherapies with demonstrated survival benefit and unclear quality-of-life benefit:● Cabazitaxel and prednisone may be offered to men who experience progression with docetaxel• Benefit: moderate; • harm: moderate to high; • evidence strength: strong; • recommendation strength:
moderate
American Society of Clinical Oncology ClinicalPractice Guideline Committee approval:April 26, 2013;
2004
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2010
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Petrylak DP, Tangen CM, Hussain MH, et al:Docetaxel and estramustinecompared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 351:1513-1520, 2004
SWOG 9916
OS 17.5 mo vs 15.6 mo
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Berthold DR, Pond GR, Soban F, et al.: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol 26:242-245, 2008
OS: median 19.2 mo vs. 17.8 mo vs 16.3 (MI arm)
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18.6% alive after 3 years
TAX 327
Adverse Reaction
TAXOTERE 75 mg/m² every 3 weeks +
prednisone 5 mg twice daily n=332
Any %Grade
3/4 %
Anemia 67 5
Neutropenia 41 32
Thrombocytopenia 3 1
Febrile neutropenia 3 N/A
Infection 32 6
Epistaxis 6 0
Allergic Reactions 8 1
Fluid Retention* 24 1
Weight Gain* 8 0
Peripheral Edema* 18 0
Neuropathy Sensory 30 2
Neuropathy Motor 7 2
Rash/Desquamation 6 0
Alopecia 65 N/A
Nail Changes 30 0
First-line docetaxel-based chemotherapy – side effects
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Adverse Reaction
TAXOTERE 75 mg/m² every 3 weeks +
prednisone 5 mg twice daily n=332
Any % Grade
3/4 %
Nausea 41 3
Diarrhea 32 2
Stomatitis/Pharyngit
is 20 1
Taste Disturbance 18 0
Vomiting 17 2
Anorexia 17 1
Cough 12 0
Dyspnea 15 3
Cardiac left
ventricular function 10 0
Fatigue 53 5
Myalgia 15 0
Tearing 10 1
Arthralgia 8 1
*Related to treatment
First-line docetaxel-based chemotherapy – side effects
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Median survival 15.1 vs 12.7 monthsHR for death 0.70 (p<0.0001)
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Median progression freesurvival 2.8 vs 1.4 months
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Short response
to ADT
• limited evidence that patients with <16 months’ response to initial androgen-deprivation therapy (ADT) may respond better to chemotherapy than subsequent hormone therapies
Gleason and docetaxel
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TAX 327
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Gleason and cabazitaxel
• Forty-seven patients • Patients received a median of nine cycles of
cabazitaxel. • Median progression-free survival was 7.0 months
(95% CI: 5.7-8.0). • At multivariate analysis, a higher Gleason score (≥
8) appeared to be associated with prolonged progression-free survival (hazard ratio: 0.36; 95% CI: 0.18-0.72);
• the higher Gleason score showed no statistical impact on overall survival.
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Buonerba C et al. Future Oncol. 2013 Jun: 9:889-97
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Short responseto ADT
• limited evidence that patients with <16 months’ response to initial androgen-deprivation therapy (ADT) may respond better to chemotherapy than subsequent hormone therapies
aggressive disease
• Gleason score ≥8 and visceral metastases – are often considered candidates for chemotherapy, although definitive data supporting this approach do not exist
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Survival according to metastatic side – TAX 327
lymph node-only metastases (median OS 26.7 months)
liver metastases with or without othermetastases median OS (10.0 months)
lung metastases with or without bone or lymph node metastases (median OS 14.4 months),
bone plus lymph node metastases (median OS 15.7 months),
bone-only metastases (median OS 19.0 months),
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Short responseto ADT
• limited evidence that patients with <16 months’ response to initial androgen-deprivation therapy (ADT) may respond better to chemotherapy than subsequent hormone therapies
aggressive disease
• Gleason score ≥8 and visceral metastases – are often considered candidates for chemotherapy, although definitive data supporting this approach do not exist
Visceralmetastases
• no comparative studies of chemotherapy and AR-targeting agents
• visceral metastases were an exclusion criterion for studies evaluating sipuleucel-T, abiraterone acetate plus prednisone in the chemotherapy-naïve setting and radium-223
Armstrong AJ et al. Clin Cancer Res 2010,16,203-211Oct-14 24ESMO preceptorship
Number of treatment cycles
Optimal duration
No survival benefit of
more than 10 cycles
Number of cycles
Pond et al. Eur Urol 2012,61,363-369Oct-14 25ESMO preceptorship
0.5 0.7 0.9 1.0 1.1 1.3 1.5
All patients
Age ≤ 68 yearsAge ≥ 69 years
PSA <115 ng/mLPSA ≥115 ng/mL
No painPain
KPS ≤80%KPS ≥90%
FACT-P <109FACT-P ≥109
Favors
Docetaxel q3w
Favors
Mitoxantrone
Berthold D et al. J. Clin. Oncol. 2008; 26:242-45
No visceral diseaseVisceral disease
Berthold D et al. J. Clin. Oncol. 2008; 26:242-45
Treatment related to age
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• 175 patients aged >75 yr with CRPC treated with first-line docetaxel
• nine French tertiary care cancer centres from 2000 to 2007.
• Median age was 78 yr.
• Ninety-five patients (54%) received a standard 3-wk regimen (SR), and 80 patients (46%) received an adapted regimen (AR)delivered on a weekly schedule with various times for rest periods
First-line docetaxel-based chemotherapy inCRPC patients aged >75 yr.
Italiano A et al. European urology 55 ( 2 0 0 9 ) 1368–1376Oct-14 27ESMO preceptorship
First-line docetaxel-based chemotherapy inCRPC patients aged >75 yr.
Italiano A et al. European urology 55 ( 2 0 0 9 ) 1368–1376
Age by itself should not be used as a criterion to deny patientswith CRPC a potentially effective chemotherapy.
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Armstrong AJ et al. Clin Cancer Res 2010,16,203-211
PSARadiologic progress.Pain progress.
Progression factors:
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Cross-resistance
It is unknown whether treating patients with hormone therapies and immunotherapies affects their subsequent response to chemotherapy
cross resistance can occur between different taxanes
between taxanes and androgen-targeting agents
between androgen-targeting agents
In vitro data have shown that docetaxel, cabazitaxel, abiraterone acetate, and enzalutamide all inhibit AR nuclear translocation
these data may have clinical implications when combining and sequencing these drugs
Mezynsky J et al. Ann Oncol 2012,23,2943-2947
PSA decline of > 50% in 9/35 ptt.
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Can androgen deprivation potentially decrease the efficacy of taxanes? Docetaxel after abiraterone
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Mezynsky J et al. Ann Oncol 2012,23,2943-2947
Docetaxel after abiraterone
PSA decline of > 50% in 9/35 ptt.
Median time to PSA progression 4.5 mo.Median overall survival 12.5 mo.
Median overall survival in the TAX 327 trial was 18.9 mo.
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Can androgen deprivation potentially decrease the efficacy of taxanes? Docetaxel after abiraterone
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Post hoc analysis abiraterone-cabazitaxel cab-abi
tumor response of both agents, particularly cabazitaxel, was lower when
administered as higher-line therapy
Abi→Cab treated patients: 6.5
months
Cab→Abi treated patients: 8.1
months
No significant diff. in OS, but in PFS
Retrospective analysis of cabazitaxel and abiraterone
63 patients received Cab→Abi(cabazitaxel prior to abiraterone) and
69 patients received Abi→Cab
Int J Cancer. 2014 Sep 20
Combination treatment
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When to start chemotherapy?
Docetaxel: adjuvant, hormone sensitive, hormone resitant
decision will be highly individualized,
based on the presence of symptoms,
comorbidities,
previous therapies,
available treatment options,
and risk of clinical progression,
patient preference based on an informed risk/benefit discussion.
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When to start chemotherapy?
Docetaxel: adjuvant, hormone sensitive, hormone resitant
Cabazitaxel: visceral metastases, only bone metastases, previous experience with chemotherapy
• FIRSTANA (NCT01308567) is a head-to-head phase III study comparing docetaxel plus prednisone with cabazitaxel plus prednisoneas first-line chemotherapy in mCRPC;
• PROSELICA (NCT01308580) is comparing twocabazitaxel doses (20 mg/m2 and 25 mg/m2) as second-line chemotherapy for mCRPC; and
• TAXYNERGY (NCT10718353) is evaluating the role of an early switch in taxane therapy based on suboptimal decline in PSA levels (<30%) within 3 months
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