Dr Kate Clarke, a member of the Gut Cancer Foundation’s Scientific Advisory Committee and current co-chair of the national gastrointestinal special interest group (GISIG) has written an open letter to Pharmac, New Zealand’s drug-buying agency, in a plea for more funding for critical drugs for cancer that has drawn the wholehearted support of the other medical practitioners in GISIG.
The gastrointestinal special interest group undertook to communicate with Pharmac on a regular basis with regards to our assessment of the landscape of systemic anti-GI cancer therapy including horizon scanning.
In 2020, we shared our priority list and added “horizon scanning.” It is notable that none of these drugs are yet funded two years later.
Our priorities in no particular order
-all ras/raf wild-type metastatic colorectal cancer
-left-sided primary tumour location
-given with first-line chemotherapy
Anti-PD-1 (e.g. pembrolizumab)
-dMMR metastatic colorectal cancer first and/or subsequent lines if not already received
-dMMR non-colon cancers
-Locally advanced not-amenable to local therapies/metastatic hepatocellular carcinoma (HCC)
-Childs-Pugh A, Barcelona stage B/C
We note Te Aho’s recent paper “Understanding the Gap” - which specifically acknowledged patients of Aotearoa/New Zealand missing out on cetuximab and atezolizumab/bevacizumab. Both have ESMO-MBCS high scores of 4 and 5 respectively. Noting that cetuximab’s score does not take into account the additional benefit of sidedness.
We also note that pembrolizumab for dMMR metastatic colon and atezolizumab/bevacizumab in HCC have received recommendations for funding with high priority from CaTSoP in July and November 2021. We wholeheartedly support our colleagues on the CaTSoP committee and applaud their hard work. We look forward to access to these innovations in a timely fashion.
Cetuximab has been caught between CaTSoP and PTAC. PTAC have declined application twice. CaTSoP have recommended funding with a medium priority. As evidence has evolved an increasingly small population with focussed survival benefit has been identified[i]. This has resulted in the use of cetuximab being restricted to left-sided primary tumour location all ras/raf wild-type cancers in international guidelines. We are in a Kafkaesque situation where one of the reasons for delay or potential decline of funding for an anti-EGFR antibody in left-sided colon cancer is that PBS (listing since 2011) NICE (listing since 2017) have not taken into account primary tumour location. We await the “options compared” process completion.
In an ideal world, Aotearoa/New Zealand patients with gastrointestinal malignancies would have access to medicines available in similar jurisdictions.
These include, but are not limited to:
-nab-paclitaxel for metastatic pancreatic adenocarcinoma,
-raltitrexed for metastatic colorectal cancer in those intolerant of/unsuitable for fluoropyrimidines
-bevacizumab for metastatic colorectal cancer
-BEACON doublet – anti-EGFR/anti-BRAF – B-RAF mutant metastatic colorectal cancer
-Anti-PD-1 for metastatic dMMR adenocarcinoma – site agnostic
As a group, we acknowledge Pharmac's funding proposal regarding biosimilar trastuzumab for those with Her-2 positive metastatic gastric cancer. The phase 3 trial demonstrating survival benefit was published in 2010 and this has been a significant gap in our resources. We welcome the opportunities that biosimilars offer and look forward to having this as an option for our patients.
Medical oncologists and nurse practitioners who treat gastrointestinal cancers continue to be frustrated by the increasing gap between what is available and funded for New Zealand patients with gastrointestinal cancers and what is available in similar jurisdictions – for example Australia’s PBS or UK’s NICE. This is now impacting on New Zealand patients’ ability to access clinical trials as the standard of care arm is frequently now not funded in GI cancers. We are barely keeping pace with the WHO’s essential medicine list.
We hold out hope for opportunities for increasing access via biosimilar cost savings.
This disparity presents challenges to patients and their whanau as self-funding at “retail” is out of the reach of most except the wealthiest including, as it must, by Ministry of Health edict, the administration costs in a private day unit also. This serves to further exacerbate the inequity in outcomes between underserved populations and the privileged.
The subsequent moral injury experienced by involved clinicians cannot be underestimated. Knowing that patients are no longer receiving cancer care as per international guidelines and being powerless to effect change is increasingly common. Please do not accept our silence as compliance.
We wanted to also draw your attention to future possibilities for patient benefit via horizon scanning.
The use of immune-oncology neo-adjuvantly is very promising and has the potential to avoid toxicity and intense therapy for the infrequent patients with colon or rectal early stage disease which is dMMR. Cercek[ii] et al., demonstrated an impressive 100% complete clinical response in those with locally advanced dMMR rectal cancer treated with six months of an anti-PD-1. This avoided chemo-radiotherapy and surgery in all patients assessed. Niche-2[iii] in which a very short course of combined anti-CTLA4/anti-PD-1 was given prior to surgery in those with dMMR colon cancer, provided a very high pathological complete response rate. Later phase trials will assist in defining how this is best integrated into treatment pathways but a new standard of care is on the way.
Adjuvant nivolumab post CROSS chemo-radiotherapy and surgery in oesophageal adenocarcinoma with residual disease at time of surgery (non-pCR) has been shown to improve disease-free survival[iv]. Overall survival analysis is still awaited.
Increasing understanding of the molecular nature of gastrointestinal stromal tumours (GISTs) also offers the opportunity of treatment rationalisation and genuine personalised medicine. This coincides with the end of the indication specific patent for imatinib (Glivec) which by allowing generic use will provide significant cost savings. Thought must be given to how to provide access to best therapy to rare subtypes within a rare disease.
Very recently published ASCO guidelines for immunotherapy and targeted therapy in advanced gastroesophageal cancer[v] provide guidance in the use of anti-PD-1 and anti-her-2 therapies in gastric and oesophageal cancers. It is notable that trastuzumab deruxtecan (an anti-her 2 cytotoxic drug conjugate) is likely to become standard of care for her-2 positive cancers in a site agnostic way e.g. gastric, colon, cholangiocarcinoma.
Yours with hope,
Dr Kate Clarke
Andrea Reilly, Clinical Nurse Specialist Cancer Coordinator
Dr Olivia Perelini
Dr Jim Edwards
Associate Professor Sharon Pattison
Dr Sarah Baird
Drumm, Oncology Nurse Practitioner
Dr Zhi Chai
Associate Professor Margaret Currie
Professor Bridget Robinson
Dr. Gaurav Gyanwali
Libby Rea Brownlee
Dr Michelle Vaughan
Dr Kirsty Danielson
Dr Marius Mathis Bartels
Dr Carmel Jacobs
Dr Laird Cameron
Dr Ben Lawrence
Dr Anna Wojtacha
Dr Simon Bann
Sarah Ellery, Nurse Practitioner
Dr Tamara Glyn
Dr Catherine Han
Te Kāhui Matepukupuku o Aotearoa, The Cancer Society of New Zealand
Dr Gwen Pinches
Dr Edmond Ang
Dr Vanessa Durandt
Dr Nikki Burnand
Rebekah Heal, General Manager, Bowel Cancer NZ
Sylvie Chan, Medical Oncology Advanced Trainee
Dr Sarah Barton
Associate Professor George Laking