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Nivolumab therapy in hepatocellular carcinoma: a clinical case

Ildiko Futo M.D.Bajcsy-Zsilinszky Hospital

Budapest, Hungary

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� 67 years old male patient� Anamnesis: hypertension (since 2009), Type 2 Diabetes

Mellitus (since 2001)� Alcohol consumption: 3-4 beers/day through 20 years.

Abstinent since february, 2016.� Elevated liver enzymes were found on a routine

laboratory test (february, 2016)� Abdominal ultrasound found a large tumour in the liver

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� Liver surgeon found thedisease inoperable (centralliver tumour in liver segment IV,V, VIII and reaches segment II-III.)

� Invasive radiologist found thedisease not eligible for localtreatment.

Liver segments 1

� CT scan revealed a 12x13 cm inhomogenous mass in theliver, dislocating the vena portae. A small subpleuralnodule (measuring 3 mm) was detected in the right lungS8. (2016 march)

� Ultrasound guided biopsy was performed from the mass,the pathology report revealed carcinoma hepatocellulare.

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� Child-Pugh A, BCLC-C� Per os multikinase-inhibitor sorafenib therapy (2x 200

mg/die) was started, but the patient experienced intolerable side effects (fatigue, weakness, hand-foot skin reaction and rash).

� Restricted to a wheelchair because of weekness� Sorafenib therapy was ended after 2 weeks.

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� Child-Pugh A, BCLC-C� Per os multikinase-inhibitor sorafenib therapy (2x 200

mg/die) was started, but the patient experienced intolerable side effects (fatigue, weakness, hand-foot skin reaction and rash).

� Restricted to a wheelchair because of weekness� Sorafenib therapy was ended after 2 weeks.

� Control CT scan (2016 june) Multiple subpleural metastasis (7-15 mm, both lungs, 10 mm in S8)The known liver mass measures 23x14 cm

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Options after sorafenib intolerance

� RegorafenibPhase III RESORCE trial: statistically and clinicallysignificant increase in overall survival from 7.8 monthswith placebo to 10.6 months with regorafenib in patientsprogressing on sorafenib. Main adverse events werehypertension, hand-foot skin reaction, fatigue anddiarrhea. 2

� Clinical trial� Off-label treatment� Best supportive care

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Options after sorafenib intolerance

� RegorafenibPhase III RESORCE trial: statistically and clinicallysignificant increase in overall survival from 7.8 monthswith placebo to 10.6 months with regorafenib in patientsprogressing on sorafenib. Main adverse events werehypertension, hand-foot skin reaction, fatigue anddiarrhea. 2

� Clinical trial� Off-label treatment� Best supportive care

Immune checkpoint blockade of the PD-1pathway offers a potential treatmentstrategy based on the encouraging resultsof the phase I/II trial of nivolumab(Checkmate 040 trial).3

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� Off-label nivolumab treatment was started based on literature data 3, 4

� Patient education� 3 mg/kg nivolumab, administered iv over 60 minutes,

every 2 weeks� Recieved 17 cycles until abstract submission� Developed CT contrast agent allergy� Regained ability to stand and walk after cycle No. 4, now

ECOG 0� Liver enzymes and AFP normalized� Tumour regression (CT scan after cycle No.14: liver

mass:9,8x7 cm, regression in the subpleural mets)� Hypomagnesemia and hyponatraemia were observed

as side effects

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100

200

300

400

500

600

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

GOT

GPT

GGT

ALP

Cycle 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Date 2016

July

20

Aug

10

Aug

24

Sept

07

Sept

22

Oct

12

Nov

02

Nov

22

Dec

06

Dec

23

2017

Jan

06

March

23

Apr

06

Apr

27

May

15

July

04

Aug

01

GOTU/l

75 61 14 12 16 14 15 16 15 14 17 21 20 29 22 19 25

GPTU/l

21 17 13 10 15 13 8 12 11 13 14 15 16 18 17 13 14

GGTU/l

349 227 95 83 75 69 62 52 47 41 44 46 47 40 39 44 37

ALPU/l

505 273 187 225 217 185 156 139 132 132 130 125 145 120 114 128 128

U/l

Cycle No.

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Date AFP ng/ml

06.04.2016. 3373

21.07.2016. >3000

12.10.2016. 59,9

06.01.2017 4,8

04.07.2017. 1,9

0

500

1000

1500

2000

2500

3000

3500

2016 April 2016 July 2016 Oct 2017 Jan 2017 July

AFP

AFP ng/ml

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Baseline CT: 23-06-2016 Control CT after cycle No. 14

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Conclusions

We achieved outstanding results in hepatocellularcarcinoma with off-label immune checkpointinhibitor therapy (nivolumab).

Not only did we find significant tumour shrinkagealong with AFP marker regression, but thenivolumab therapy also positively affected thepatients’ quality of life. The side effects weremanageable and tolerable.

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References

� 1: http://www.stefajir.cz/?q=liver-segments-sonography� 2: Rimassa L, Pressiani T, Personeni N, Santoro A. Regorafenib for the

treatment of unresectable hepatocellular carcinoma. Expert Rev AnticancerTher. 2017 Jul;17(7):567-576.

� 3: Melero I, Crocenzi TS, Welling TH, Yau TC, Yeo W, Chopra A, Grosso J,Lang L, Anderson J, Dela Cruz CM, Sangro B. Phase I/II safety andantitumor activity of nivolumab in patients with advanced hepatocellularcarcinoma (HCC): CA209-040. J Clin Oncol. 2015 Jun 20;33 (18_suppl):LBA101.

� 4: Kudo M. Immune Checkpoint Blockade in Hepatocellular Carcinoma.Liver Cancer. 2015 Dec;4(4):201-7

e-mail: Ildi.futo@gmail.com

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