Living Longer: Advanced Stage Liver Cancer (BCLC C)

Introduction

Unfortunately, more than 2/3 of liver cancer patients are diagnosed at advanced stage liver cancer (BCLC C).

Advanced stage liver cancer (BCLC C) consist(s) of:

  • invasion into major liver blood vessels or/ and
  • spread beyond the liver (lung, lymph nodes).

Patients in BCLC C group will benefit from systemic treatment (also suitable for BCLC B patients who are not suitable for chemo-embolisation).

Most systemic treatments require preserve liver function, Child Pugh Class A (or selected Child Pugh Class B).

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Barcelona Clinic Liver Cancer (BCLC) staging system
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Child Pugh Class A: Good liver function

First Line Treatment

There was only one recommended systemic treatment for liver cancer throughout my training period.

The first line treatment using  sorafenib (Nexavar), a targeted therapy inhibiting pathway of cancer growth was well established since 2008

  • SHARP trial (sorafenib vs placebo) reported improvement in survival 10.7 months vs 7.9 months.
  • Asia-Pacific phase 3 trial (sorafenib vs placebo), median survival 6.5 months vs 4.2 months.

In 2018, after 10 long years, another treatment, lenvatinib,  was made available in first line setting.

  • Lenvatinib was approved in 1st line treatment on the basis that it is not inferior to Sorafenib.
  • Positive result from REFLECT trial (lenvatinib vs sorafenib), reported median survival of 13.6 months vs 12.3 months.

Selective internal radiation therapy (SIRT) using yttrium-90 resin microspheres injected into the tumors had been compared in first line setting also.

  • SARAH trial compare the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) with yttrium-90 (90Y) resin microspheres
  • Median overall survival was 8 months (SIRT group) vs 9.9 months in (sorafenib group) but statistically, no significant different.
  • SIRT was found to be slightly more tolerable than systemic treatment using sorafenib
Selective-internal-radiation-therapy(1000x800).jpg
Selective internal radiotherapy (SIRT)

Second Line Treatment

After failure of first line treatment, approved second line treatments are:

  • Regorafenib (RESOURCE trial; R vs placebo), median survival 10.6 months vs 7.8 months (must be tolerable to sorafenib in 1st line)
  • Carbozantinib (CELESTIAL trial; C vs placebo), median survival 10.2 months vs 8 months
  • Ramucirumab (REACH-2 trial; R vs placebo), median survival 7.8 months vs 4.2 months
  • Pembrolizumab (KEYNOTE-224 trial; phase II), median survival 9.4 months.
    • Phase 3 KEYNOTE-240 trial in progress: results pending

UPDATE 5/4/2018

  • Nivolumab (CHECKMATE-040 trial; phase I/II), median survival 15 months.
    • Phase 3 CHECKMATE-459 (first line) trial in progress: results pending
  • Durvalumab (phase I/II study), median survival 13.2 months.

Palliative Care

Early palliative care referral is indicated for patients with end stage liver function/ those who is not a candidate for liver transplant (BCLC D) and those who failed second line systemic treatment.

Patient should continue treatments if treatments are still available and patient is still fit.

Palliative radiotherapy, although not proven to increase survival, could be used to improve some symptoms like bleeding or pain caused by the gastric mass. It is much tolerable than palliative chemotherapy.

With adequate treatment, I hope symptoms will only come at late stage and patients suffering will be a brief one before passing away.

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