1. Unità Dipartimentale di Oncologia IRCCS Fondazione S. Maugeri
Esperienza Real Life
Raffaella Palumbo
Unità Dipartimentale di Oncologia
IRCCS Fondazione S. Maugeri
PAVIA

2. Evidence-based medicine does not make
clinical practice … … … people do
WHY REAL LIFE ?
Aiming to provide a picture of “real life clinical practice”
“Moving beyond clinical trials: real life treatment
with albumin-bounded paclitaxel (nab-paclitaxel) in MBC
A multicenter Italian experience”
RETROSPECTIVE ANALYSIS
We analyzed the different patterns of treatment and outcome of women receiving single-agent Nab-P for their MBC in 9 Centers of North Italy
Patient and tumour characteristics and treatment-related variables were summarized using descriptive statistics, including median and range; the chi-square test was used to compare categorical variables, and p≤0.05 was considered statistically significant
A subgroup analysis was performed to identify potential prognostic and/or predictive factors for disease outcome and treatment response
Progression-free survival (PFS) and overall survival (OS) were calculated according to the Kaplan-Meyer method
We analyzed the different patterns of treatment and outcome of women receiving single-agent Nab-P for their MBC in 9 Centers of North Italy
Patient and tumour characteristics and treatment-related variables were summarized using descriptive statistics, including median and range; the chi-square test was used to compare categorical variables, and p≤0.05 was considered statistically significant
A subgroup analysis was performed to identify potential prognostic and/or predictive factors for disease outcome and treatment response
Progression-free survival (PFS) and overall survival (OS) were calculated according to the Kaplan-Meyer method

3. FOCUS ON … … … WHY REAL LIFE ? A ‘difficult-to-treat’ population
“Prospective evaluation of activity, safety and quality of life of
nab-paclitaxel as 2nd line chemotheraphy in taxane-pretreated disease”
PROSPECTIVE STUDY
To evaluate the performance of single-agent Nab-P in women who at the time of disease relapse had yet received the most active agent in the neo-adjuvant setting,
ie conventional taxane
available data from retrospective or post-hoc analysis
no informations regarding QoL

4. DIFFERENT PATTERNS OF TREATMENT WITH
ACTIVITY AND SAFETY OF ALBUMIN–BOUND PACLITAXEL (NAB-PACLITAXEL) IN SECOND AND FURTHER LINES OF CHEMOTHERAPY FOR METASTATIC BREAST CANCER PATIENTS: A TWO-YEAR MULTICENTER ITALIAN EXPERIENCE
R. Palumbo1, M.E. Cazzaniga2, E. Simoncini3, C. Tondini4, E. Piazza5, A. Ferzi6, D. Grasso7, M. Danova7, E. Tarenzi8,
F. Sottotetti1, F. Villa2, E. Rota Caremoli4, P. Poletti4 A. Gambaro3, F. Tosi3, C. Fasola3,
C. Cavalli7, M. Torchio7, V.Gambi8, A.Bernardo1
1Deparmental Unit of Oncology-IRCCS Maugeri Foundation, Pavia; 2Medical Oncology-San Gerardo Hospital, Monza;3Breast Unit, Brescia; 4Medical Oncology-Papa Giovanni XXIII Hospital, Bergamo; 4MedicalOncology-Luigi Sacco Hospital, Milano; 6Medical Oncology-Legnano Hospital; 7Medical Oncology-IRCCS San Matteo Hospital, Pavia; 8Medicine and Oncology Unit-Vigevano Hospital, Pavia; 9Medical Oncology-Falck, Ca’ Granda Hospital, Milano
DIFFERENT PATTERNS OF TREATMENT WITH
ALBUMIN–BOUNDED PACLITAXEL (NAB-PACLITAXEL) FOR TARGETED CHEMOTHERAPY IN METASTATIC BREAST CANCER PATIENTS: A MULTICENTER ITALIAN EXPERIENCE ON 125 WOMEN
TARGETED CHEMOTHERAPY WITH ALBUMIN-BOUND PACLITAXEL
(NAB-PACLITAXEL) FOR METASTATIC BREAST CANCER (MBC):
A REAL WORLD MULTICENTER ITALIAN EXPERIENCE ON 180 WOMEN

5. DATA ANALYSIS
180 women treated at 9 Italian Institutions from February 2011 were included in the analysis, with cut-off data evaluation as of September 2014
Final analysis on the overall population of 215 women included, cut-off data evaluation as of December 2014
submitted
TREATMENT SCHEDULES
Patients received Nab-P as monotherapy intravenously over 30 minutes at the dose of 260 mg/m2 every 3 weeks or 125 mg/m2 weekly at the discretion of the treating oncologist
Steroid premedication was not required before therapy infusion
Treatment was given in the outpatient setting up to disease progression or unacceptable toxicity or patient refusal

6. STUDY POPULATION (1) q3w Nab-P 260 mg/m2 qw Nab-P 125 mg/m2 OVERALL
No of patients (%)
95 (52.7)
85 (47.2)
180 (100)
Median age, years [range]
<65 years
≥65 years
52 [33-68]
67 (70.5)
28 (29.4)
54 [45-82]
41 (48.2)
44 (51.7)
54 [33-82]
108 (60.0)
72 (40.0)
ECOG Performance Status 1 2
49 (51.5)
34 (35.7)
12 (12.6)
32 (37.6)
29 (34.1)
24 (28.2)
81 (45.0)
63 (35.0)
36 (20.0)
Primary tumour subtype
Luminal A
Luminal B
Triple negative
30 (31.5)
39 (41.0)
26 (27.3)
34 (40.0)
22 (25.8)
64 (35.5)
68 (37.7)
48 (26.6)
Prior systemic therapy (early stage)
anthracycline-based CT (no taxane)
anthracycline + taxane
taxane only
CMF
43 (45.2)
33 (34.7)
11 (11.5)
8 (8.4)
30 (35.2)
10 (11.7)
4 (4.7)
84 (46.6)
21 (11.6)
12 (6.6)
Median DFI, months (range)
≤24 months
>24 months
42 (19-96)
37 (38.9)
58 (61.0)
49 (42-134)
33 (38.8)
52 (68.2)
46 (19-134)
70 (38.0)
110 (61.0)

7. STUDY POPULATION (2) q3w Nab-P 260 mg/m2 qw Nab-P 125 mg/m2 OVERALL
No of patients (%) 95 85
180
Prior CT for metastatic disease
taxane-based
without taxane
68 (71.5)
27 (28.4)
39 (45.8)
46 (54.1)
107 (59.4)
73 (40.5)
Median n°of prior CT lines for metastatic disease (range)
1 prior CT line
2 prior CT lines
3 prior CT lines
≥4 CT lines
3 (1-5)
46 (48.4)
25 (26.3)
16 (16.8)
8 (8.40)
4 (2-8)
29 (34.1)
21 (24.7)
19 (22.3)
16 (18.8)
3 (1-8)
75 (44.0)
46 (20.6)
35 (18.6)
24 (13.3)
Visceral involvement
45 (52.9)
113 (62.7)
Dominant metastatic sites
liver
lung
bone/nodes
skin/soft tissues
38 (40.0)
30 (31.5)
11 (11.5)
26 (30.5)
25 (29.4)
15 (17.6)
64 (35.5)
49 (27.2)
41 (22.7)
26 (14.4)
Number of metastatic sites 1 2 ≥3
14 (14.7)
18 (18.9)
63 (66.3)
32 (37.6)
46 (25.5)
44 (24.4)
90 (50.0)
CT: chemotherapy

8. TREATMENT ACTIVITY q3w Nab-P n = 95 qw Nab-P n = 85 OVERALL n = 180
Objective RR (%)
50 (52.6)
30 (35.23)
80 (44.4)
Complete response
Partial response
Stable disease ≥16 weeks
Progression disease
8 (8.40)
42 (44.2)
29 (30.5)
16 (16.8)
5 (3.00)
25 (29.4)
30 (29.5)
25 (17.6)
13 (7.20)
67 (37.2)
59 (32.7)
41 (22.7)
Clinical Benefit rate
(CR+PR+SD ≥16 weeks)
79 (83.1)
60 (70.5)
139 (77.2)
Median follow-up
Median PFS in the whole population
Median PFS in 2nd line subgroup
Median PFS in ≥3rd line subgroup
18 months (range 6-30)
7.8 months (range 3-23+)
12.9 months (range 6-23+)
4.8 months (range 3-8.8)

9. TREATMENT TOXICITY q3w Nab-P n = 95 qw Nab-P n = 85 OVERALL n = 180
WHO grade 3 4
n (%)
Anemia
3 (1.60) -
Leukopenia
14 (14.7)
7 (7.30)
4 (4.7)
18 (10.0)
7 (3.80)
Neutropenia
28 (29.4)
18 (18.9)
12 (14.1)
5 (5.80)
40 (22.2)
23 (12.7)
Thrombocytopenia
Diarrhea
2 (2.10)
Nausea/vomiting
3 (3.15)
2 (2.35)
5 (2.77)
Mucositis
1 (1.50)
3 (1.66)
Fatigue
4 (4.21)
6 (3.33)
Sensory neuropathy
15 (17.6)
8 (12.3)
Hypersensitivity reactions
Alopecia **
68 (71.5)
3 (3.52)
71 (39.4)
** grade 1-2 in all patients in the q3w cohort

10. TREATMENT COMPLIANCE
q3w Nab-P
n = 95
qw Nab-P
n = 85
OVERALL
n = 180
Median n° of cycles
(range)
6 (3-27)
5 (3-18)
Required dose reduction
[n (%)]
17 (17.8)
11 (12.9)
28 (15.5)
Median treatment duration
[months (range)]
8 (6-21)
6 (4-15)
6 (4-21)
No significant differences in toxicity profile in the ≥65 years old patients (40%)

11. RESPONDING PATIENTS ACCORDING TO BASELINE CHARACTERISTICS
SUBGROUP ANALYSIS (1)
RESPONDING PATIENTS ACCORDING TO BASELINE CHARACTERISTICS
Variable
N°of patients OR
n (%)
95% CI CB
180
80 (44.4)
139 (77.2)
Age
<65 years
≥65 years
108 72
47 (43.5)
33 (45.8)
88 (81.4)
51 (70.8)
DFI
≤24 months
>24 months 70
110
34 (48.5)
46 (41.8)
58 (82.8)
81 (73.6)
Previous adjuvant CT
taxane-based
without taxanes 84 96
37 (40.4)
43 (44.7)
69 (82.1)
70 (72.9)
Metastatic disease sites
viscera
other
113 67
51 (45.1)
29 (43.2)
89 (78.7)
50 (74.6)
OR: Objective Responses; CB: Clinical Benefit

12. RESPONDING PATIENTS ACCORDING TO BASELINE CHARACTERISTICS
SUBGROUP ANALYSIS (2)
RESPONDING PATIENTS ACCORDING TO BASELINE CHARACTERISTICS
Variable
N°of patients OR
n (%)
95% CI CB
180
80 (44.4)
139 (77.2)
Number of involved sites
1-2 ≥3 90
46 (51.6)
34 (37.7)
64 (71.1)
69 (76.6)
Previous CT for metastatic disease
taxane-based
without taxanes
107 73
48 (44.8)
32 (43.8)
81 (75.7)
58 (79.4)
Nab-paclitaxel schedule
3-weekly
weekly 95 85
49 (51.5)
31 (34.1)
81 (82.1)
58 (68.2)
Nab-paclitaxel line of treatment
2nd line
3rd or more lines 75
105
50 (66.6)
30 (28.5)
68 (90.6)
71 (67.6)
OR: Objective Responses; CB: Clinical Benefit

13. NAB-PACLITAXEL
IN TAXANE-PRETREATED MBC

14. NAB-PACLITAXEL
IN TAXANE-PRETREATED MBC

15. IN TAXANE-PRETREATED MBC
NAB-PACLITAXEL
IN TAXANE-PRETREATED MBC
median number of given cycles: 6 (range 4-27)
92% of patients received nab-P at the protocol-specified dose and 40% of them had ≥9 cycles;
median relative DI: 98%
G-CSF support given in 5 women during 8 cycles of treatment; administration delayed by one week in 9/52 patients
onset of sensory neuropathy after a median of 6 cycles (range 3-14)
median time to improvement to a lower grade: 19 days (16-26)

16. IN TAXANE-PRETREATED MBC
NAB-PACLITAXEL
IN TAXANE-PRETREATED MBC
No need for premedication and short-term infusion allowed good patient compliance in the whole population. Information on treatment tolerability was available for all the treated patients (Table 5). ‘Very good’ tolerability was reported in 28%-33% of the patients receiving nab-paclitaxel compared to 19% for last therapy, while the percentage of patients reporting ‘insufficient’ tolerability did not exceed 6%. Overall, 60% of all the patients reported an improvement in tolerability of nab-paclitaxel compared with their last therapy, mostly from ‘satisfactory’ to ‘good’ or from ‘good’ to ‘very good’.

17. No need for premedication and short-term infusion allowed good patient compliance in the whole population
60% of all the patients reported an improvement in tolerability of nab-P compared with their last therapy, mostly from ‘satisfactory’ to ‘good’ or from ‘good’ to ‘very good’

18. STUDY KEY POINTS
Our “real world” experience, consistent with efficacy published results, confirm that Nab-paclitaxel is a valid chemotherapy option as second and further chemotherapy line in MBC, also for patients pretreated with taxane in the adjuvant and/or metastatic setting
Both the 3-weekly and weekly schedules produced encouraging ORR, PFS and CB values, with globally manageable toxicities and good patient compliance in the outpatient setting, in women given long-term treatment too
For clinicians, in the daily decision making, the chance of a flexible schedule of administration allows a better targeted therapeutic approach to each woman at the different points of her history, basing on both the disease-related factors and patient attitudes

19. NAB-PACLITAXEL REAL LIFE EXPERIENCES
Ottawa Hospital cancer center Ontario 42 pts da giugmo 2006 a dicembre 2010
Weekly NAB 13.6 months and 10.8 months for q3w (p=0.03)
17.3. months for women achieving CB and 7.7 for non CB (p=0.001)
British Columbia 132 pa (122 per analisi) dal 2007 al 2011 British Columbia CANADA
No substantial difference in median TTF for the group with ptior taxane-exposure compared with the non-exposure group (96 days versus 73.5 days, p=0.58)
Espeienz aIndian su 43 pz q3w
Aigner J, Marmé F, Smetanay K, Schuetz F, Jaeger D, Schneeweiss A 
Nab-Paclitaxel monotherapy as a treatment of patients with metastatic breast cancer in routine clinical practice.
Anticaner Res 33(8): , 2013
RK Singh, S Pankaj, S Kumar, V Rajkota
A Retrospective Study of Efficacy and Safety of Albumin-Bound Paclitaxel in Metastatic Breast Cancer
Worl J Oncol 5: , 2014

20. WHICH SCHEDULE FOR WHICH PATIENTS ? q3w Nab-Paclitaxel
age <65 years
DFI ≤24 months
triple negative subtype
predominant visceral disease
qw Nab-Paclitaxel
age ≥65 years
<2 metastatic sites
no visceral involvement
ongoing trials
investigating potentially predictive biomarkers
of treatment response and disease outcome

21. THANK YOU Medical Oncology-San Gerardo Hospital, Monza
Breast Unit, Brescia
Medical Oncology-Luigi Sacco Hospital, Milano
Medical Oncology-Papa Giovanni XXIII Hospital, Bergamo
Medical Oncology-Legnano Hospital
Medical Oncology-IRCCS San Matteo Hospital, Pavia
Medicine and Oncology Unit-Vigevano Hospital, Pavia
Medical Oncology-Falck, Ca’ Granda Hospital, Milano
Deparmental Unit of Oncology-IRCCS Maugeri Foundation, Pavia