clinicians' views on introducing epidermal growth factor receptor testing in new zealand

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ORIGINAL ARTICLE Clinicians’ views on introducing epidermal growth factor receptor testing in New Zealand Lesley S BATTEN, 1 Helen S WINTER, 2 Claire L HARDIE 2 and Maureen A HOLDAWAY 1 1 Research Centre for Ma ¯ ori Health and Development, Massey University and 2 Regional Cancer Treatment Service, MidCentral District Health Board, Palmerston North, New Zealand Abstract Aim: Inequities exist in the outcomes of patients diagnosed with lung cancer in New Zealand, with Ma ¯ori (the indigenous population) having significantly higher diagnosis rates and poorer survival. We investigated the feasibility of introducing epidermal growth factor receptor (EGFR) testing into New Zealand as one step to address these inequities. Methods: An anonymous electronic questionnaire was distributed to clinicians from specialties involved in lung cancer management. Questions were grouped around topics including challenges in lung cancer management, EGFR testing, targeted therapy, costs and interest in the development of a national lung tissue bank. Results: In total, 61 clinicians responded and noted that few of their non-small-cell lung cancer patients were tested for EGFR mutations. Most clinicians (84%) would prefer a centralized testing service and 95% would use an overseas laboratory if publicly funded; however 62% did not know or had no preference for test procedures. Under half (46%) had used tyrosine kinase inhibitors with only a small number of patients and 79% supported the development of a lung tissue bank. Conclusion: While most respondents had little experience with EGFR testing, clinicians supported its introduction into New Zealand. However, a number of potential issues, including cost, laboratory expertise and the need for improved access to first-line targeted therapies that could be used if tests were mutation positive were also identified. Respondents identified potential cultural sensitivities related to sending tissue samples abroad for genetic tests that would necessitate clinicians discussing this option with individual patients. Key words: epidermal growth factor receptor, New Zealand, non-small-cell lung cancer, survey. INTRODUCTION In New Zealand lung cancer is the leading cause of cancer death, with new registrations of cancer of the trachea, bronchus and lung being the fifth most common site, and female registration rates increasing by 27% between 1998 and 2008. 1 Rates of lung cancer registra- tion of new cancers and of deaths for Ma ¯ori, the indig- enous population, are considerably higher than for non- Ma ¯ ori, with Ma ¯ ori male rates double, and Ma ¯ ori female Correspondence: Dr Lesley Batten PhD, Research Centre for Ma ¯ori Health and Development, Massey University, Private Bag 11 222, Palmerston North 4442, New Zealand. Email: [email protected] Research support This research was funded by the Health Research Council of New Zealand (HRC 10/675). Conflict of interest: none Accepted for publication 12 August 2012. Asia-Pacific Journal of Clinical Oncology 2013; 9: 249–256 doi: 10.1111/ajco.12012 © 2012 Wiley Publishing Asia Pty Ltd

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Page 1: Clinicians' views on introducing epidermal growth factor receptor testing in New Zealand

ORIGINAL ARTICLE

Clinicians’ views on introducing epidermal growth factorreceptor testing in New Zealand

Lesley S BATTEN,1 Helen S WINTER,2 Claire L HARDIE2 andMaureen A HOLDAWAY1

1Research Centre for Maori Health and Development, Massey University and 2Regional Cancer Treatment Service, MidCentralDistrict Health Board, Palmerston North, New Zealand

Abstract

Aim: Inequities exist in the outcomes of patients diagnosed with lung cancer in New Zealand, with Maori(the indigenous population) having significantly higher diagnosis rates and poorer survival. We investigatedthe feasibility of introducing epidermal growth factor receptor (EGFR) testing into New Zealand as one stepto address these inequities.

Methods: An anonymous electronic questionnaire was distributed to clinicians from specialties involvedin lung cancer management. Questions were grouped around topics including challenges in lung cancermanagement, EGFR testing, targeted therapy, costs and interest in the development of a national lung tissuebank.

Results: In total, 61 clinicians responded and noted that few of their non-small-cell lung cancer patientswere tested for EGFR mutations. Most clinicians (84%) would prefer a centralized testing service and 95%would use an overseas laboratory if publicly funded; however 62% did not know or had no preference fortest procedures. Under half (46%) had used tyrosine kinase inhibitors with only a small number of patientsand 79% supported the development of a lung tissue bank.

Conclusion: While most respondents had little experience with EGFR testing, clinicians supported itsintroduction into New Zealand. However, a number of potential issues, including cost, laboratory expertiseand the need for improved access to first-line targeted therapies that could be used if tests were mutationpositive were also identified. Respondents identified potential cultural sensitivities related to sending tissuesamples abroad for genetic tests that would necessitate clinicians discussing this option with individualpatients.

Key words: epidermal growth factor receptor, New Zealand, non-small-cell lung cancer, survey.

INTRODUCTION

In New Zealand lung cancer is the leading cause ofcancer death, with new registrations of cancer of thetrachea, bronchus and lung being the fifth most commonsite, and female registration rates increasing by 27%between 1998 and 2008.1 Rates of lung cancer registra-tion of new cancers and of deaths for Maori, the indig-enous population, are considerably higher than for non-Maori, with Maori male rates double, and Maori female

Correspondence: Dr Lesley Batten PhD, Research Centre forMaori Health and Development, Massey University, PrivateBag 11 222, Palmerston North 4442, New Zealand.Email: [email protected]

Research supportThis research was funded by the Health Research Council ofNew Zealand (HRC 10/675).

Conflict of interest: none

Accepted for publication 12 August 2012.

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Asia-Pacific Journal of Clinical Oncology 2013; 9: 249–256 doi: 10.1111/ajco.12012

© 2012 Wiley Publishing Asia Pty Ltd

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rates more than four and a half times that of non-Maori.2 Compared to similar countries, lung cancer sur-vival statistics for New Zealand are poor across allpopulation groups3 and divergences from internationaltreatment recommendations have been identified.4 Inaddition, Maori experience disparities in relation tostage at diagnosis, access to curative therapies andtransit times from diagnosis to treatment.5,6

Currently there is no publicly funded testing for epi-dermal growth factor receptor (EGFR) mutations inlung cancer patients, and the mutation rates in the totalpopulation or any subgroups are unknown. We canassume that the New Zealand European populationis likely to have a low mutation rate, as found inother predominantly European popuations;7 however,no ethnic group comparable to Maori has been tested.The tyrosine kinase inhibitor (TKI) erlotinib waspublicly funded for those with advanced, unresectablenon-small-cell lung cancer (NSCLC) from October2010. However, only those with disease progressionafter first-line treatment with platinum-based chemo-therapy are eligible.8 A positive EGFR mutation statuswas not required, and EGFR testing is not yet men-tioned in the “Standards of Service Provision for LungCancer Patients in New Zealand”.9

While investigating the feasibility of introducingEGFR testing for patients with NSCLC, and specificallyfor Maori patients, in New Zealand, we surveyed clini-cians involved in the diagnosis and management of lungcancer to ascertain their views on and experiences withEGFR testing, TKI therapies and the potential develop-ment of a national lung cancer tissue bank.

METHODS

The survey received ethical approval (MEC/10/088/EXP) from the Multi-region Ethics Committee. Datawere collected over a 3-month period in 2011. Theself-completion, anonymous survey included bothopen and closed questions and was piloted. Questionsincluded clinicians’ perspectives and experiences ofEGFR testing, including taking additional samples,preferred testing processes and acceptable costs andexperiences with TKI therapy. With their informedconsent, the clinicians’ details were collected, as weretheir impressions of the challenges of lung cancer man-agement in New Zealand. The survey was administeredvia SurveyMonkey and a preliminary descriptive analy-sis was undertaken using this tool, with additionaldescriptive statistical analyses and content analyses of

open questions undertaken using Microsoft Excel(Microsoft, New York, USA).

Participants and sampling

Clinicians (physicians, pathologists and public andprivate pathology services) involved in the diagnosisand treatment of lung cancer throughout New Zealandwere surveyed, using purposive sampling. With permis-sion, questionnaires were distributed electronically to anumber of professional e-lists. Hard copies of the ques-tionnaire were also distributed at a national lung cancersymposium. As the e-lists were moderated by their asso-ciated organizations and it was possible that some cli-nicians were members of a number of e-lists, we couldnot ascertain the number of clinicians who were sent thesurvey invitation.

A total of 61 clinicians responded. The samplecomprised medical oncologists and registrars (43%),respiratory physicians (25%), radiation oncologists andregistrars (11%), pathologists (7%) and others, includ-ing those who did not identify their specialty (15%). Ofthis number 73% were male, and 59% identified withan ethnicity of New Zealand European (respondentscould affiliate with multiple ethnicities and those listedincluded Maori, Samoan, Chinese, British and Indian.)Staff from 12 of the 20 district health boards (DHB)were represented; however, 25% of participants did notidentify their board. Of the 55 clinicians who answeredthe question, 30% had worked in their specialty forfewer than 5 years.

RESULTS

Involvement with NSCLC

Among the clinicians who answered the question (ninedid not) 40% had diagnosed or treated 6–20 NSCLCpatients in the previous 12 months, 35% had diagnosedor treated 21–50 patients and 11% had diagnosed ortreated 50 or more patients. Maori patients withNSCLC ranged from fewer than 5% of all patients (for14% of clinicians who answered the question), 6–15%(39%), and 16–25% (31%) to more than 25% of allpatients (17% of clinicians).

An important health issue?

Respondents were asked a set of questions to gauge theirperspectives of lung cancer, targeted therapy and EGFRtesting. In all, 61% of respondents “strongly agreed”that the treatment of lung cancer with targeted therapy

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is an important heath issue, 35% “moderately agreed”and 3% were “neutral”. No respondents disagreed.

The role of EGFR testing in the

management of NSCLC patients

Respondents were asked to identify potential rolesfor EGFR testing in lung cancer. Three respondents(5%) considered that there was no role for EGFR testingin NSCLC patients (Table 1). Non-smokers or distantex-smokers with adenocarcinomas were the “other”patient groups identified.

Experience with EGFR testing for NSCLC

Although EGFR testing is currently not publicly fundedin New Zealand, at the time of this survey some sampleswere being sent overseas for testing on patient request oras part of a clinical trial. In addition, some respondentshad worked overseas in environments where EGFRtesting was undertaken. Few respondents (28%, n = 17)had actual experience with ordering or undertakingEGFR tests. The circumstances respondents identifiedwhen they had ordered or undertaken EGFR testingfor NSCLC patients included patients wanting TKI asfirst-line therapy, following decisions by a hospital lungmultidisciplinary cancer meeting and for second-linetherapy for selected groups (Table 2).

Percentages of NSCLC patients being

tested for EGFR mutations

To gauge the percentage of NSCLC patients currentlybeing tested for EGFR mutations, respondents who hadsome experience with EGFR testing were asked whatpercentage of their patients had undergone an EGFRtest in the previous 12 months and, in the same timeperiod, the percentage of their Maori patients tested.In all, 55 respondents answered these questions. The

results were very similar (Table 3): 96% of these respon-dents answered that less than 10% of all of their NSCLCpatients had been EGFR tested and 98% answered thatless than 10% of their Maori patients with NSCLChad been tested. A small number (4% for all NSCLCpatients and 2% for Maori patients with NSCLC)reported that 11–30% of their patients with NSCLChad been tested for EGFR mutations.

Interest in a New Zealand EGFR testing

service and challenges of testing overseas

Some clinicians are currently accessing overseas EGFRtesting services. We were interested in the level ofsupport for the development of a testing service in NewZealand and if so, whether this should be a centralizedor regional service. There was significant support (84%)for a centralized service, with only 12% of respondentswanting each DHB to arrange its own. Few (5%) wereunsure or answered “no”.

When asked if they would access a funded overseasservice if none was available in New Zealand, 95% ofrespondents answered they would. However, whenasked whether sending samples for testing overseaswould create any specific difficulties, a wide range ofchallenges were selected, with only 24% of respondentsidentifying no difficulties. The length of time it would

Table 1 Do you think there is a role for introducing epider-mal growth factor receptor (EGFR) testing in non-small-celllung cancer (NSCLC) patients?

Role of EGFR testing (multipleresponses possible)

Response %(n = 61)

Yes, for lung adenocarcinomas 46Yes, for all palliative NSCLC patients

undergoing active treatment31

Yes, for research purposes 26Yes, for all NSCLC patients at any stage 26Yes, for other patients 3No 5

Table 2 Experience with epidermal growth factor receptor(EGFR) testing for non-small-cell lung cancer (NSCLC)

Circumstances (multipleresponses possible)

Response (%, n)(N = 65)

I have heard about it but not ordered/undertaken EGFR tests

66 (40)

I have arranged/undertaken this in certaincircumstances

28 (17)

I have arranged/undertaken this for trialpatients

7 (4)

I have not heard of it 5 (4)I have a protocol for doing this routinely 0

Table 3 In the last 12 months what % of your non-small-celllung cancer (NSCLC) patients have had an epidermal growthfactor receptor (EGFR) test? (%, n)

Precentage of patients All patients Maori patients

Less than 10 96 (53) 98 (54)11–30 4 (2) 2 (1)31–100† 0 0†Scale combined as no responses.

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take to receive the results (48%, n = 29) and difficultiesfor clinicians (44%, n = 26) and pathologists (41%,n = 24) were the most frequently selected responses.However, cost implications (34%, n = 20) and difficul-ties for all patients (25%, n = 15) were also identified.A small number of responses (19%, n = 11) related topotential difficulties for some ethnic groups if sampleswere sent overseas.

Respondents who selected “Yes, for some ethnicgroups” were asked to specify the groups. Seven ofthe nine responses identified Maori, and/or Pacificpeople, acknowledging recognized cultural sensitivitiesaround the care of tissue samples. One respondentstated, “Maori would need to have tissue returned if[they] wished”, necessitating a “need to discuss this[sending tissue samples overseas] individually with thepatient”. One respondent commented: “ethnic groupsare irrelevant”.

Preferred EGFR test

Most respondents (62%, n = 38) did not know whattype of EGFR test technique they preferred, while 25%(n = 15) noted a preference for DNA sequencing and10% (n = 6) preferred commercial test kits.

Disadvantages to offering testing in New

Zealand to NSCLC patients

We wished to ascertain clinicians’ views of possibledisadvantages if routine EGFR testing was made avail-able. While four respondents provided no answer, 39%(n = 22) identified no disadvantages. However, otherrespondents were concerned about excessive costs(35%, n = 20) and the lack of local expertise (32%,n = 18). Another major disadvantage respondents notedwas the ethical issue of testing for EGFR mutationswhen the corresponding targeted therapy was unfunded.One respondent stated: “Current issues with fundedtargeted therapies – shouldn’t do a test routinely unlesswe can offer appropriate treatment”. Other disadvan-tages included the “need for biopsies”, “false negativesand adverse consequences of tissue acquisition” and thatas “the main groups of mutations are already known,selective testing is required”.

Additional biopsy samples

EGFR tests are usually performed on formalin-fixed paraffin embedded or fresh frozen tumor tissuesamples. Internationally, work is underway to explorethe reliability of undertaking EGFR testing on circulat-ing tumor cells and other tissue. Insufficient samples,

precluding testing, is a common problem, so we askedrespondents if they would be prepared to arrange foradditional biopsy samples for EGFR testing. Over half(57%) would do this for “all NSCLC patients suitablefor active therapy”. However, 33% identified concernsfor some patient groups, related to patient factors (e.g.frail patients), diagnosis (e.g. patients not fitting theclinical phenotype) and TKI response (those withoutclinical indicators of a likely TKI response, e.g., heavysmokers).

Results turnaround

Results are crucial for clinical decision-making anddelays to initiation of therapy while awaiting results isan issue, especially in cases of aggressive disease.10

Therefore, we asked respondents what constituted anacceptable time frame for the turnaround of EGFR testresults. Most (61%, n = 36) selected an acceptable timeperiod of 1–2 weeks with 15% (n = 9) identifying up toa week, and 24% (n = 14) considering 2–4 weeks asappropriate. The turnaround time for tests sent overseaswas also raised as a concern (in a previous question) by48% of respondents.

Acceptable cost

Currently, EGFR tests are not publicly funded in NewZealand, although some patients pay privately and sometesting is undertaken as part of clinical drug trials, paidfor by the pharmaceutical company. Respondents wereasked what they considered an appropriate cost, irrespec-tive of payer, and 36% considered NZ$200–$400 appro-priate, while 18% saw costs as unimportant (Fig. 1).

Respondent experience with using

targeted therapy for NSCLC treatment

Targeted therapy with a TKI (erlotinib) is used in NewZealand in clinical trials, and has recently been publicly

Figure 1 Acceptable cost of an EGFR test, irrespective ofpayer.

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funded as second-line therapy. We were interested inrespondents’ levels of experience with using targetedtherapy. Nearly half of the respondents (46%, n = 26)had used targeted therapy for only a small number ofNSCLC patients, with 30% (n = 17) having no experi-ence of using it.

Patient advice regarding the response rate

(RR) (%) to erlotinib

The advice clinicians provide to patients about the asso-ciation between the presence of EGFR mutations andthe likely RR to erlotinib represents clinicians’ knowl-edge of current research. We provided respondents withthree scenarios: 1, “no EGFR test undertaken”; 2, in the“presence of EGFR mutation” and, 3, in the “absence ofEGFR mutation” to explore what advice clinicianswould give to patients with NSCLC regarding the RR(%) to erlotinib. Most respondents identified the correctRR of 10–20% for scenario 1 (87%, n = 43) and70–80% for scenario 2 (62%, n = 31). There was lesscertainty about RR in the absence of an EGFR muta-tion, with 53% (n = 26) of respondents selecting 0%,and 47% (n = 23) selecting 10–20%, when currentresearch identifies a RR of 10% for this patient group.10

Current challenges in the clinical

management of NSCLC

We were interested in what respondents saw as currentchallenges in the clinical management of NSCLC toascertain other complexities in lung cancer treatment.Respondents were asked two questions regarding thesechallenges, one relating to all patients and the secondspecifically for Maori patients. Respondents could makemultiple selections from a range of responses (Fig. 2) aswell as documenting other challenges.

Written comments regarding the “other” categoryincluded 14 comments for all patients and 16 commentsspecifically for Maori patients. While there was someoverlap in the comments for both groups, additionalchallenges were related to Maori patients. For allpatients, factors reflected health sector issues, such asthe need for access to palliative care in acute services,and rapid assessment and initiation of treatment. Thechallenges for treatment of Maori NSCLC patientsrelated to sociocultural and economic factors that deter-mine access to services, such as culturally accessibleservices and travel costs, as well as distance from treat-ment centers. Other factors were cultural perspectives,such as the need for extended family support and the useof traditional medicines.

Support for a national lung cancer

tissue bank

Respondents were asked if they were in favor of thedevelopment of a centralized, national lung cancer tissuebank. Most (79%) supported the concept, while only5% did not support it and 16% did not respond. Thosewho did not support the concept argued that it would becomplex and expensive to develop, and one respondentassumed there would be cultural resistance to keepingtissue samples. Supporters identified benefits for currentand future lung cancer research, the ability to identifyvariations in special populations, including differencesrelated to ethnicity, and the value of consistent data.

Familiarity with other molecular tests

in NSCLC

Finally, as the understanding of the molecular basis oflung cancer and resistance to targeted therapies israpidly evolving, we asked respondents to rate their levelof familiarity with a variety of molecular tests relevantto NSCLC (Table 4). Except for KRAS (v-Ki-ras2Kirsten rat sarcoma viral oncogene homolog), of which35% (n = 19) reported being “somewhat familiar”,most respondents reported being “not at all familiar”with the other tests (ERCC1 [excision repair cross-complementation group 1], RRM1 [ribonucleotidereductase M1] and ALK-fusion).

DISCUSSION

Currently in New Zealand there is no publicly fundedEGFR testing service for NSCLC patients. Most of the

Figure 2 Current challenges in the clinical management ofNSCLC for ( ) Maori patients and ( ) all patients. CT, com-puted tomography; PET positron emission tomography.

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clinicians surveyed would support establishment of sucha service and favored a national, centrally located NewZealand service. However, clinicians would use overseaslaboratories if they were publicly funded. Ideally,respondents considered that test results should be avail-able within 2 weeks; the test should cost less thanNZ$400 and it should be offered to all NSCLC patientsor to all patients with a diagnosis of lung adenocarci-noma. In all 57% of respondents were willing to orga-nize additional biopsies for EGFR testing for patientssuitable for active therapy.

However, few of the respondents had organized anEGFR test for a NSCLC patient and few patients hadundergone EGFR testing, which appears to be at oddswith practice in similar countries. This is probablybecause in New Zealand EGFR-directed therapy forNSCLC patients has only recently been publicly funded,and only after the failure of first-line chemotherapy.

Why is this issue important? EGFR testing andEGFR-targeted therapy are yet to be included in the“Standards of Service Provision for Lung CancerPatients in New Zealand”.9 In the UK, however, theNational Institute for Health and Clinical Excellence(NICE) guidance on gefitinib notes that “gefitinib isrecommended as an option for the first-line treatment ofpeople with locally advanced or metastatic non-small-cell lung cancer (NSCLC) if: they test positive for theepidermal growth factor receptor tyrosine kinase(EGFR-TK) mutation”11 (p. 4). In addition, this guid-ance stipulates that “testing for EGFR mutations shouldbe carried out on all eligible patients irrespective of theirgender, ethnicity, and smoking status to ensure that allpatients who could benefit from gefitinib are identi-fied”11 (p. 38). These recommendations stem from datasupporting the effectiveness of EGFR TKI therapy inthis context and its financial benefit to the NationalHealth Service compared to the use of chemotherapy inNSCLC patients who are EGFR mutation positive.

Molecularly targeted therapies directed at the EGFRreceptor, such as the TKIs erlotinib and gefitinib, are

more effective if the EGFR receptor is mutated.12 Studiesalso indicate that in patients with an EGFR mutation,an EGFR TKI is a more effective treatment than chemo-therapy.13,14 This was confirmed in a meta-analysis of13 trials comparing EGFR TKI therapy versus standardchemotherapy in NSCLC patients with mutatedEGFR.15 This potential ability to more accurately directeffective treatments could reduce the financial costs ofless effective treatment and the burden of patients oftreatment failure. However in New Zealand, there is norequirement to determine EGFR mutation status beforeprescribing erlotinib as second-line therapy. In addition,we do not know the EGFR mutation rate in NewZealand of any of our ethnic groups. It may be that inthe New Zealand European population the mutationrate is relatively low as in other predominantly Euro-pean populations,7 whereas there has been no study ofEGFR mutation rates with a readily comparable ethnicgroup to Maori to estimate their mutation rate. Wewould argue therefore that a more cost effectiveapproach would be to determine EGFR mutation statusin New Zealand NSCLC patients to guide appropriatesystemic therapy and reduce the burdens of treatmentsunlikely to be of benefit, as per the NICE guidance in theUnited Kingdom. This might open the way to publiclyfunded EGFR TKI therapy as a first-line treatment forpatients with an EGFR mutation, given that data nowsupports the use of these drugs for these patients.13 Sucha funding change would also partially mitigate theethical concern of performing a test for a therapy thatis currently only publicly funded second-line in NewZealand.

Clinicians’ familiarity with molecular tests used inNSCLC demonstrates the challenges respondents’ expe-rience with maintaining their knowledge in an areawhere the scientific knowledge is rapidly evolving andthe translation of research findings to clinical practice isalways complex. We focused on four tests and respon-dents demonstrated different levels of familiarity witheach. These four molecular tests, in combination with

Table 4 Familiarity with other molecular tests in non-small-cell lung cancer (NSCLC (%))

Clinicians’ self-ranking ERCC1 (n = 54) RRM1 (n = 54) KRAS (n = 55) ALK-fusion (n = 54)

Very familiar 7 6 16 9Somewhat familiar 15 9 35 28Only heard of it 35 26 31 28Not familiar at all 43 59 18 35

ALK-fusion, fusion gene comprising portions of the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphomakinase (ALK) gene; ERCC1, excision repair cross-complementation group 1; KRAS, Ki-ras2 Kirsten rat sarcoma viral oncogene homolog; RRM1,ribonucleotide reductase M1.

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EGFR, provide a more detailed picture of the patho-genesis of NSCLC and probable responses to targetedtherapies. For example, KRAS and EGFR are the twomost commonly mutated oncogenes in lung cancer andstudies have shown that while those tumors with anEGFR mutation show increased sensitivity to TKIs,those with KRAS mutations “fail to benefit from adju-vant chemotherapy, and their disease does not respondto EGFR inhibitors”16 (p. 201). Patients whose tumorsexpress EGFR mutations are a distinct group from whothat harbor the EML4-ALK fusion gene and there ispotential for ALK inhibitors to improve patient out-comes for this group.17 Significantly prolonged survivalhas been found in patients with completely resectedNSCLC treated with cisplatin-based adjuvant chemo-therapy whose tumors were ERCC1-negative whencompared to those whose tumors were ERCC1 posi-tive.18 Other studies have identified a strong correlationbetween ERCC1 and RRM1, with “concomitant lowexpression levels of ERCC1 and RRM1 predictive of abetter outcome”19 (p. 1818).

This survey formed part of a larger study that focusedon exploring appropriate processes for engaging Maoripatients in the use of targeted therapies and EGFRtesting, with the overall aim of reducing health inequi-ties experienced by Maori with lung cancer. We weretherefore interested in clinicians’ perspectives on themanagement of tissue samples, and in particular if cli-nicians commented, without prompting, about Maoricultural protocols related to the samples. Other authorshave identified specific cultural protocols for handlingsamples and involving Maori in research processes.20

Whereas some clinicians recognized that Maori patientsmay be uncomfortable with tissue samples being sentabroad or stored in tissue banks, others assumed that allMaori patients would be uncomfortable and that thiswould block their engagement in EGFR testing. Impor-tantly, a small number of clinicians noted that discus-sions should be held individually with each patient toascertain their views, rather than making assumptionsthat in turn may limit patients’ access to potentiallybeneficial testing and treatments.

The small number of respondents is a study limita-tion. We distributed the survey electronically throughprofessional organizations and therefore cannot beprecise as to the total number of clinicians questioned.However, we do know that 60 radiation oncologistsand registrars were contacted, of whom 15 replied. Thisresults in a 25% RR, which, we suggest, may not be verydissimilar in other specialties. We acknowledge that theresults may not reflect the views of all New Zealand

clinicians involved in the diagnosis and management oflung cancer. However, there is regional representationin the responses from New Zealand as a whole. Therespondents were drawn from the range of clinicianspecialties, except for cardio-thoracic surgeons, that areinvolved in the multidisciplinary management of lungcancer. If we were to repeat this survey it would beuseful to liaise with the recently formed New ZealandNational Lung Cancer Working Group to organize dis-tribution to clinicians actively involved in the manage-ment of lung cancer.

In conclusion, our survey results indicated thatEGFR mutation status testing was perceived as impor-tant in the management of lung cancer. However, anumber of potential issues, including cost, laboratoryexpertise and the need for improved access to first-linetargeted therapies that could be used if tests weremutation positive were also identified. Respondentsidentified potential cultural sensitivities related tosending tissue samples from Maori and Pacific peoplesabroad for EGFR testing that would necessitate clini-cians discussing this option with individual patients.Further research is needed to identify whether Maorimay benefit from EGFR testing and targeted therapyas a way of reducing the health inequities they alreadyexperience.

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Since submission of this article the researchers have welcomedthe decision of the Pharmaceutical Management Agency ofNew Zealand (PHARMAC) to fund first-line EGFR targetedtherapy for those patients who test as EGFR positive.PHARMAC have recommended that this testing be funded byDHBs, and many have already agreed to do so.

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