Aportación del lenvatinib al tratamiento del carcinoma ... · Aportación del lenvatinib al...

Aportación del lenvatinib al tratamiento del carcinoma

hepatocelularDr. Javier Sastre

Servicio de Oncologia Médica

HC San Carlos

Lenvatinib

Tumour cell

VEGF

Lenvatinib

VEGF-receptor (1-3)

1. Stjepanovic N and Capdevila J. Biologics 2014;8:129–139.2. http://www.selleckchem.com/datasheet/E7080-DataSheet.html#s_ref (Accessed December 2017).

3. EMA Lenvatinib EPAR http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/003727/WC500188676.pdf (Accessed February 2018).

PDGFPDFG-receptor

FGF receptor (1-4)

RETIC502,3:• VEGFR1 = 22 nM• VEGFR2 = 4.0 nM• VEGFR3 = 5.2 nM• Ret = 6.4 nM• PDGFR-α = 51 nM• PDGFR-β = 39 nM• FGFR1 = 61 nM• FGFR2 = 27 nM• FGFR3 = 52 nM• FGFR4 = 43 nM• KIT = 100 nM

• Lenvatinib (E7080) is an oral multiple receptor tyrosine kinase inhibitor targeting VEGFR-1-3, FGFR-1-4, RET, c-KIT, and PDGFR-beta1

• Lenvatinib potently inhibits FGFR-1, offering a potential opportunity to block one of the well known mechanisms of resistance to VEGF/VEGFRinhibitors1

c-KIT

Lenvatinib: Phase I MTD and Dose-finding Study

• 20 patients (9 in CP-A and 11 in CP-B) were enrolled

The MTD was 12 and 8 mg once daily (QD) in CP-A and CP-B, respectively

• DLTs included proteinuria, hepatic encephalopathy, and hyperbilirubinemia

• The most common grade 3/4 toxicities (any dose) included hypertension, hyperbilirubinemia, increased AST and proteinuria

• Lenvatinib plasma concentration at 24 hours after administration (C24 h) for 12 mg QD was higher in patients with HCC compared with other solid tumours (phase I study)

• C24 h for 25 mg once daily lenvatinib was comparable with the 12mg CP-A group

Ikeda M et al. Clin Cancer Res. 2016;22: DOI: 10.1158/1078-0432.CCR-15-1354.

Lenvatinib Phase II Study: Design

• Aim: Assess the antitumor activity and safety of lenvatinib in patients with advanced HCC

Patients with advanced HCC (N=46) • ≥1 measurable target

lesion• 1–3 tumour lesions [>3

cm in diameter ([>5 cm diameter if only one lesion) or ≥ 4 lesions or portal vein invasion, extrahepatic invasion

• ECOG 0 or 1• Child-Pugh class A• Hepatectomy and local

therapy received for at least 6 and 4 weeks respectively

Lenvatinib12 mg PO QD, 28-day cycles

Ikeda K et al. J Gastroenterol. 2017; 52:512–19.

Primary endpoint Time to progression (mRECIST)

Secondary endpointsObjective response rateType of progressive diseaseDisease control rateOverall survivalSafetyPharmacokinetic

Lenvatinib Phase II Study: Baseline Data


Patient Characteristics (N = 46)

Median age, yrs (range) 66.5 (37-80)

Sex, n (%)FemaleMale

13 (28.3)33 (71.7)

Region, n (%)JapanSouth Korea

43 (93.5)3 (6.5)

Median weight, kg (range) 56.7 (42.8-85.5)

ECOG PS, n (%)01

38 (82.6)8 (17.4)

Child-Pugh class, n (%)AB

45 (97.8)1 (2.2)

BCLC staging, n (%)BC

19 (41.3)27 (58.7)

Portal vein invasion, n (%)YesNo

5 (10.8)41 (89.1)

Patient Characteristics (N = 46)

Extrahepatic metastases, n (%)YesNo

21 (45.7)25 (54.3)

Cause of HCC, n (%)Hepatitis BHepatitis CAlcoholNAFLDUnknown

15 (32.6)27 (58.7)

2 (4.3)1 (2.2)2 (4.3)

AFP value at baseline, n (%)<200 ng/ml≥200 ng/ml

27 (57.7)18 (39.1)

Prior surgery for HCC, n (%)NoYes

27 (58.7)19 (41.3)

Prior local therapy, n (%)NoYesRFAPEITACETAE

4 (8.7)42 (91.3)32 (69.6)12 (26.1)39 (84.8)

3 (6.5)

Prior chemotherapy, n (%)SorafenibOtherHepatic intra-arterial chemotherapy

6 (13.0)5 (10.9)5 (10.9)

Lenvatinib Phase II Study: Efficacy Data (Response Rate)

Parameter, n (%) Investigator assessment (mRECIST), n=46

IRRC assessment (mRECIST), n=46

IRRC assessment (RECIST 1.1), n=46

Best response

Complete response 0 0 0

Partial response 17 (37) 17 (37) 11 (24)

Stable disease 21 (46) 19 (41) 25 (54)

Progressive disease 5 (11) 6 (13) 6 (13)

Not evaluable 3 (7) 4 (9) 4 (9)

Objective response rate 17 (37) 17 (37) 11 (24)

Disease control rate 38 (83) 36 (78) 36 (78)

IRRC, independent radiologic review committee; mRECIST, modified response evaluation criteria in solid tumors.


Lenvatinib Phase II Study: Efficacy Data (TTP and OS)


Median TTP was 7.4 months Median OS was 18.7 months

0

Est

imate

d p

robabilit

y (

%)

0

20

40

60

80

100

0

Est

imate

d p

robabilit

y (

%)

0

20

40

60

80

100

2 4 6 8 10 12 14 16 18 20 2 4 6 8 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 4410

Survival time (months)TTP (months)

46 35 31 20 15 10 9 5 2 1 0 46 45 45 40 39 31 27 27 24 21 17 14 13 13 11 10 10 9 5 4 3 03300000000IRR

No. at Risk

12 mg

Lenvatinib

No. at Risk

IRR Assessment

Censored Observations

12 mg Lenvatinib

Censored Observations

Lenvatinib Phase II Study: Efficacy Data (Best Overall Response)

60

40

20

0

-20

-40

-60

-80

-100

80

Ch

ange

fro

m b

asel

ine

(%)

Best overall response

PR (n=17)

SD (n=19)

PD (n=6)

NE (n=3)

*


Lenvatinib Phase II Study: Safety (1)Adverse event, n (%) All grades, n=46 Grade 3, n=46 Grade 4 (n = 46)

Hypertension 35 (76.1) 25 (54.3) 0

PPE syndrome 30 (65.2) 4 (8.7) 0

Decreased appetite 28 (60.9) 1 (2.2) 0

Proteinuria 28 (60.9) 9 (19.6) 0

Fatigue 25 (54.3) 0 0

Diarrhoea 20 (43.5) 6 (13.0) 0

Constipation 19 (41.3) 0 0

Nausea 17 (37.0) 1 (2.2) 0

Dysphonia 17 (37.0) 0 0

Thromobcytopenia 16 (34.8) 9 (19.6) 1 (2.2)

Peripheral oedema 16 (34.8) 0 0

Decreased weight 14 (30.4) 2 (4.3) 0

Neutropenia 13 (28.3) 2 (4.3) 0

Nasopharyngitis 13 (28.3) 0 0

Rash 13 (28.3) 0 0


Lenvatinib Phase II Study: Safety (2)

Adverse event, n (%) All grades, n=46 Grade 3, n=46 Grade 4 (n = 46)

Increased blood thyroid-stimulating hormone level

12 (26.1) 0 0

Back pain 11 (23.9) 0 0

Stomatitis 11 (23.9) 0 0

Vomiting 11 (23.9) 1 (2.2) 0

Pyrexia 10 (21.7) 0 0

Hypothyroidism 10 (21.7) 0 0

Insomnia 10 (21.7) 0 0


Lenvatinib Phase II Study: Conclusions

• Median TTP was 7.4 months [95 % CI 5.5–9.4]

• 37 % of patients had partial response and 41 % had stable disease (DCR: 78 %)

• Median OS was 18.7 months (95 % CI 12.7–25.1)

• The most common AEs were hypertension (76 %), palmar-plantar erythrodysesthesia syndrome (65 %), decreased appetite (61 %), and proteinuria (61 %)

• Dose reductions and discontinuations due to AEs occurred in 34 (74 %) and 10 patients (22 %), respectively

Lenvatinib 12-mg QD showed clinical activity and acceptable toxicity profiles in patients with advanced HCC; however early dose modification was necessary in

patients with lower body weight


12

• Median TTP was 7.4 months [95 % CI 5.5–9.4]

• 37 % of patients had partial response and 41 % had stable disease (DCR: 78 %)

• Median OS was 18.7 months (95 % CI 12.7–25.1)

• The most common AEs were hypertension (76 %), palmar-plantar erythrodysesthesiasyndrome (65 %), decreased appetite (61 %), and proteinuria (61 %)

• Dose reductions and discontinuations due to AEs occurred in 34 (74 %) and 10 patients (22 %), respectively

Lenvatinib Phase II Study: Conclusions

Lenvatinib 12-mg QD showed clinical activity and acceptable toxicity profiles in patients with advanced HCC; however early dose modification was necessary in

patients with lower body weightIkeda K et al. J Gastroenterol. 2017; 52:512–19.

Training HCC – Module 4 Internal Ipsen

13

Lenvatinib Phase III Non-inferiority Study: Design

Kudo M et al. Lancet. 2018 Feb 9. pii: S0140-6736(18)30207-1. [Epub ahead of print].

Patients with advanced HCC (N=954) • No prior systemic therapy• ≥1 measurable target lesion• BCLC stage B or C• ECOG 0 or 1• Child-Pugh class A• Adequate organ function

Lenvatinib (n=478)8 mg (bodyweight <60 kg) or 12 mg

(bodyweight ≥60 kg) PO QD

Primary endpoint Overall survival

Secondary endpointsProgression-free survivalTime to progressionObjective response rateQuality of lifePharmacokinetics

Sorafenib (n= 476)400 mg PO BID

1:1

Stratified by geography (Asia vs Western); macrovascular invasion and/or extrahepatic

disease; ECOG PS (0 vs 1); Bodyweight (<60 kg vs ≥60 kg)

Aim: To assess the efficacy of lenvatinib vs sorafenib in the first-line treatment of patients with unresectable HCC

Open-label, phase 3, multicentre, non-inferiority trial


14

Lenvatinib Phase III Non-inferiority Study: Baseline Data (1)

Patient Characteristics, n (%) Lenvatinib (n = 478) Sorafenib (n = 476) Total (n = 954)

Median age, years (range) 63.0 (20-88) 62.0 (22-88) 62.0 (20-88)

Sex MaleFemale

405 (85)73 (15)

401 (84)75 (16)

806 (84)148 (16)

Region WesternAsia-Pacific

157 (33)321 (67)

157 (33)319 (67)

314 (33)640 (67)

Race WhiteAsianOther

135 (28)334 (70)

9 (2)

141 (30)326 (68)

9 (2)

276 (29)660 (69)

18 (2)

Body weight <60 kg≥60 kg

153 (32)325 (68)

146 (31)330 (69)

299 (31)655 (69)

ECOG PS 01

304 (64)174 (36)

301 (63)175 (37)

605 (63)349 (37)

Child-Pugh class AB

475 (99)3 (1)

471 (99)5 (1)

946 (99)8 (1)

Macrovascular invasion (MI) Yes No

109 (23)369 (77)

90 (19)386 (81)

199 (21)755 (79)

Extrahepatic spread (EHS) Yes No

291 (61)187 (39)

295 (62)181 (38)

586 (61)368 (39)

MI, EHS or both Yes No

329 (69) 149 (31)

336 (71) 140 (29)

665 (70)289 (30)

Underlying cirrhosis (masked, independent review)

YesNo

356 (74)122 (26)

364 (76)112 (24)

720 (75)234 (25)



15

Lenvatinib Phase III Non-inferiority Study: Baseline Data (2)

Patient Characteristics, n (%) Lenvatinib (n = 478) Sorafenib (n = 476) Total (n = 954)

BCLC staging BC

104 (22)374 (78)

92 (19)384 (81)

196 (21)758 (79)

Involved disease sites LiverLung

441 (92)163 (34)

430 (90)144 (30)

871 (91)307 (32)

Involved disease sites per patient

12≥3

207 (43)167 (35)103 (22)

207 (43)183 (38)86 (18)

414 (43)350 (37)189 (20)

Aetiology of chronic liver disease

Hepatitis BHepatitis CAlcoholOtherUnknown

251 (53)91 (19)36 (8)38 (8)

62 (13)

228 (48)126 (26)

21 (4)32 (7)

69 (14)

479 (50)217 (23)

57 (6)70 (7)

131 (14)

Baseline AFP concentration (ng/ml)

Patients, n (%)Mean (SD)Median (IQR)

471 (99)17507.5 (105137.4)133.1 (8.0-3730.6)

463 (97)16678.5 (94789.5)71.2 (5.2-1081.8)

934 (98)17096.5 (100088.8)

89.0 (6.3-2120.2)

Baseline AFP concentration group, ng/ml

<200≥200Missing

255 (53)222 (46)

1 (<1)

286 (60)187 (39)

3 (1)

541 (57)409 (43)

4 (<1)

Concomitant systemic antiviral therapy for hepatitis B or C, n (%)

163 (34) 149 (31) 312 (33)

Previous therapy Previous anticancer proceduresRadiotherapy

327 (68)

49 (10)

344 (72)

60 (13)

671 (70)

109 (11)



16

Lenvatinib Phase III Non-inferiority Study: Efficacy (Primary Endpoint OS)

0 3 6 9 12 15 18 2421 3630 42

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.0

1.0

Pro

bab

ility

Time (months)

27 3933

Number at riskLenvatinib 478 436 374 297 253 207 178 140 102 67 40 21 8 2 0

Sorafenib 476 440 348 282 230 192 156 116 83 57 33 16 8 4 0

Median (month) (95% CI)

Lenvatinib 13.6 (12.1–14.9)

Sorafenib 12.3 (10.4–13.9)

HR (95% CI): 0.92 (0.79–1.06)



17

Lenvatinib Phase III Non-inferiority Study: Efficacy(OS Sub-group Analysis)

Characteristic SubgroupEvents/Patients HR (95% CI)

Lenvatinib vs Sorafenib

Median (months)

Lenvatinib Sorafenib Lenvatinib Sorafenib

Overall 351/478 350/476 0.92 (0.79-1.06) 13.6 12.3

Age< 65 y≥ 65y

203/270148/208

204/283146/193

0.94 (0.77-1.15)0.84 (0.66-1.07)

12.414.6

11.413.4

SexMaleFemale

293/40558/73

293/40157/75

0.91 (0.77-1.07)0.84 (0.56-1.26)

13.415.3

12.411.4

RegionAsia-PacificWestern

243/321108/157

248/319102/157

0.86 (0.72-1.02)1.08 (0.82-1.42)

13.513.6

11.014.2

ECOG-PSPS = 0PS = 1

221/304130/174

223/301127/175

0.88 (0.73-1.06)0.97 (0.76-1.25)

14.610.7

12.810.3

Body weight< 60 kg≥ 60 kg

110/153241/325

113/146237/330

0.85 (0.65-1.11)0.95 (0.79-1.14)

13.413.7

10.312.5

MVI, EHS or bothYesNo

250/329101/149

259/33691/140

0.87 (0.73-1.04)1.05 (0.79-1.40)

11.518.0

9.818.0

AFP at baseline< 200 ng/mL≥ 200 ng/mL

167/255183/222

193/286154/187

0.91 (0.74-1.12)0.78 (0.63-0.98)

19.510.4

16.38.2

EtiologyHBVHCV

196/25975/103

186/24497/135

0.83 (0.68-1.02)0.91 (0.66-1.26)

13.415.3

10.214.1

BCLC stagingStage BStage C

71/104280/374

65/92285/384

0.91 (0.65-1.28)0.92 (0.77-1.08)

18.511.8

17.310.3

Posttreatmentanticancer therapy

YesNo

143/206208/272

175/243175/233

0.84 (0.67-1.06)0.91 (0.74-1.11)

19.510.5

17.07.9

Favors Lenvatinib Favors Sorafenib0.5 21



18

Lenvatinib Phase III Non-inferiority Study: Efficacy (Secondary Endpoint PFS by mRECIST)

0 3 6 9 12 15 18 2421 3630 42

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.0

1.0

Pro

bab

ility

Time (months)

27 3933

Number at riskLenvatinib 478 345 223 172 106 69 44 28 14 9 4 2 0 0

Sorafenib 476 262 140 94 56 41 33 22 14 9 4 2 2 0


Lenvatinib 7.4 (6.9–8.8)

Sorafenib 3.7 (3.6–4.6)

HR (95% CI): 0.66 (0.57–0.77)Log-rank Test: p-value: <0.0001



19

Lenvatinib Phase III Non-inferiority Study: Efficacy (PFS Sub-group Analysis)

Characteristic SubgroupEvents/Patients HR (95% CI)

Lenvatinib vs Sorafenib

Median (months)

Lenvatinib Sorafenib Lenvatinib Sorafenib

Overall 349/478 367/476 0.66 (0.57-0.77) 7.4 3.7

Age< 65 y≥ 65y

201/270148/208

223/283144/193

0.67 (0.55-0.82)0.61 (0.48-0.78)

7.37.4

3.65.4

SexMaleFemale

293/40551/73

308/40159/75

0.66 (0.56-0.77)0.75 (0.49-1.13)

7.47.4

3.74.6

RegionAsia-PacificWestern

249/321100/157

264/319103/157

0.61 (0.51-0.73)0.81 (0.61-1.08)

7.37.4

3.65.5

ECOG-PSPS = 0PS = 1

220/304129/174

233/301134/175

0.63 (0.52-0.76)0.70 (0.55-0.90)

7.47.3

3.73.7

Body weight< 60 kg≥ 60 kg

111/153238/325

121/146246/330

0.61 (0.46-0.79)0.69 (0.58-0.83)

7.47.4

3.63.7

MVI, EHS or bothYesNo

246/329103/149

265/336102/140

0.64 (0.54-0.77)0.73 (0.55-0.97)

7.39.2

3.65.6

AFP at baseline< 200 ng/mL≥ 200 ng/mL

186/255163/222

209/286157/187

0.68 (0.55-0.83)0.59 (0.47-0.75)

9.05.5

5.42.4

EtiologyHBVHCV

205/25970/103

199/244103/135

0.62 (0.50-0.75)0.78 (0.56-1.09)

7.37.4

3.65.3

BCLC stagingStage BStage C

72/104277/374

66/92301/384

0.70 (0.50-0.99)0.63 (0.53-0.75)

9.17.3

5.53.7

Posttreatmentanticancer therapy

YesNo

177/206172/272

204/243163/233

0.58 (0.47-0.72)0.70 (0.56-0.87)

7.28.0

3.63.7

Alcohol 19/33 18/23 0.27 (0.11–0.66) 8.8 3.9

Favors Lenvatinib Favors Sorafenib0.5 21


0.1


20

Lenvatinib Phase III Non-inferiority Study: Efficacy (Secondary Endpoint TTP)

0 3 6 9 12 15 18 2421 3630 42

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.0

1.0

Cu

mu

lati

ve p

rogr

essi

on

rat

e

Time (months)

27 3933

Number at riskLenvatinib 478 341 218 170 106 69 43 28 14 9 4 2 0 0

Sorafenib 476 258 139 94 55 41 33 22 14 9 4 2 2 0


Lenvatinib 8.9 (7.4–9.2)

Sorafenib 3.7 (3.6–5.4)

HR (95% CI): 0.63 (0.53–0.73)Log-rank Test: P-value: <0.00001



21

Lenvatinib Phase III Non-inferiority Study: Maximum Change in Tumour Size (investigator assessed per mRECIST)

Lenvatinib (n = 478) Sorafenib (n = 476) Effect size p value

Median OS, months95% CI

13.6 12.1-14.9

12.3 10.4-13.9

HR 0.92 (0.79–1.06) -

Median PFS, months95% CI

7.4 6.9-8.8

3.7 3.6-4.6

HR 0.66 (0.57–0.77) <0.0001

Median TTP, months95% CI

8.9 7.4-9.2

3.7 3.6-5.4

HR 0.63 (0.53–0.73) <0.0001

ORR, n (%)95% CI

115 (24.1)20.2–27.9

44 (9.2)6.6–11.8

OR 3.13 (2.15–4.56) <0.0001

CR 6 (1) 2 (<1) - -

PR 109 (23) 42 (9) - -

SD 246 (51) 244 (51) - -

Durable SD 167 (35) 139 (29) - -

PD 71 (15) 147 (31) - -

Unknown/NE 46 (10) 41 (9) - -

DCR, n (%)95% CI

361 (75.5)71.7–79.4

288 (60.5)56.1–64.9

- -



22

Lenvatinib Phase III Non-inferiority Study: Maximum Change in Tumour Size (masked, independent review per mRECIST)

Lenvatinib (n = 478) Sorafenib (n = 476) Effect size p value

Median PFS, months95% CI

7.35.6–7.5

3.63.6–3.7

HR 0.64 (0.55–0.75) <0.0001

Median TTP, months95% CI

7.47.2-9.1

3.7 3.6-3.9

HR 0.60 (0.51–0.71) <0.0001

ORR, n (%)95% CI

194 (40.6)36.2–45.0

59 (12.4)9.4–15.4

OR 5.01 (3.59–7.01) <0.0001

CR 10 (2) 4 (1) - -

PR 184 (38) 55 (12) - -

SD 159 (33) 219 (46) - -

Durable SD 84 (18) 90 (19) - -

PD 79 (17) 152 (32) - -

Unknown/NE 46 (10) 46 (10) - -

DCR, n (%)95% CI

353 (73.8)69.9–77.8

278 (58.4)54.0–62.8

- -



23

Lenvatinib Phase III Non-inferiority Study: Safety (treatment-emergent AEs)

Overview of TEAEs, n(%) Lenvatinib (n = 476) Sorafenib (n = 475)

Treatment-emergent adverse events (TEAEs)

Any TEAETreatment-related TEAE

470 (99)447 (94)

472 (99)452 (95)

Any TEAE ≥ grade 3Treatment-related TEAE ≥ grade 3

357 (75)270 (57)

316 (67)231 (49)

Any serious AETreatment-related serious TEAE

205 (43)84 (18)

144 (30)48 (10)

Dose modifications

Drug interruption due to related TEAEs 190 (40) 153 (32)

Dose reduction due to related TEAEs 176 (37) 181 (38)

Drug discontinuations due to related TEAEs 42 (9) 34 (7)



24

Lenvatinib Phase III Non-inferiority Study: Safety (most frequent TEAEs)

AE ≥15% of patients, n (%) Lenvatinib (n=476) Sorafenib (n = 475)

Any grade Grade 3/4 Any grade Grade 3/4

Hypertension 201 (42) 111 (23) 144 (30) 68 (14)

Diarrhoea 184 (39) 20 (4) 220 (46) 20 (4)

Decreased appetite 162 (34) 22 (5) 127 (27) 6 (1)

Decreased weight 147 (31) 36 (8) 106 (22) 14 (3)

Fatigue 141 (30) 18 (4) 119 (25) 17 (4)

Palmar-plantar erythordysesthesia 128 (27) 14 (3) 249 (52) 54 (11)

Proteinuria 117 (25) 27 (6) 54 (11) 8 (2)

Dysphonia 113 (24) 1 (<1) 57 (12) 0

Nausea 93 (20) 4 (1) 68 (14) 4 (1)

Decreased platelet count 87 (18) 26 (5) 58 (12) 16 (3)

Abdominal pain 81 (17) 8 (2) 87 (18) 13 (3)

Hypothyroidism 78 (16) 0 8 (2) 0

Vomiting 77 (16) 6 (1) 36 (8) 5 (1)

Constipation 76 (16) 3 (1) 52 (11) 0

Elevated AST 65 (14) 24 (5) 80 (17) 38 (8)

Rash 46 (10) 0 76 (16) 2 (<1)

Alopecia 14 (3) 0 119 (25) 0

Increased bilirubin 71 (15) 31 (7) 63 (13) 23 (5)



25

Lenvatinib Phase III Non-inferiority Study: Health-related quality of life

Baseline scores on the EORTC QLQ-C30 and HCC-specific QLQ-HCC18 questionnaires were similar between the lenvatinib- and sorafenib-treated patients• Following treatment, scores declined in both treatment groups

Compared with lenvatinib-treated patients, it was observed that those treated with sorafenib experienced (nominal p<0.05):

• Earlier worsening of role functioning, pain, and diarrhoea scores from QLQ-C30

• Earlier deterioration of nutrition and body image from QLQ-HCC18



26

• Lenvatinib demonstrated non-inferiority versus sorafenib in OS in patients with unresectable HCC (13.6 months vs 12.3 months, for lenvatinib and sorafenib respectively)

• Lenvatinib treatment resulted in statistically significant improvements in PFS, TTP, ORR vs sorafenib

• The safety profiles of lenvatinib was consistent with the known safety profiles of this TKI in HCC

• No new safety signals were reported for either agent

Lenvatinib Phase III Non-inferiority Study: Conclusions

Lenvatinib may be a potential first-line systemic treatment option in patients with advanced, unresectable HCC



Phase Ib Lenvatinib + Pembrolizumab

Ikeda et al. @ASCO 2018

A Phase 1b Trial of Lenvatinib (LEN) Plus Pembrolizumab

in Patients With Unresectable HCC

ORR: 42%

Lenvatinib combination ongoing phase III trials: Trial design

AdvancedHCC & VHB infection

1:1

Nivolumab 480 mg every 4w

+

Lenvatinib 12 mg/day

(8mg in < 60Kg)


(8mg in < 60Kg)

Treatment until disease

Progression or unaceptable

toxicity

Primary objective:Overall survival

Secondary objectives:PFSResponse rateToxicity and Quality of Live

216 ptes

ClinicalTrials.gov Identifier: NCT04044651

Lenvatinib combination ongoing phase III trials: Trial design

AdvancedHCC 1:1

Pembrolizumab 200 mg every 3w

+


(8mg in < 60Kg)


(8mg in < 60Kg)

Treatment until disease

Progression or unaceptable

toxicity

Primary objective:Overall survivalPFS

Secondary objectives:Response rateToxicity and Quality of LivePharmacokinetic assessment

750 ptes

ClinicalTrials.gov Identifier: NCT03713593

Aportación del lenvatinib al tratamiento del carcinoma ... · Aportación del lenvatinib al...

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