Summary: cost consequences of FGFR2 testing and of diagnostic delay

Eligibility for lirafugratinib requires identification of an FGFR2 fusion or rearrangement, and the guideline recommendation for molecular analysis in advanced disease applies to all participants suitable for systemic treatment. The yield of testing is low relative to the number tested: in 91 biliary tract tumours profiled at one centre, potentially actionable alterations were found in 23.1% and genomically matched therapy was introduced in 7.7%, and FGFR2 fusions or rearrangements occur in approximately 9% of profiled cholangiocarcinomas. The Canadian drug agency estimated that testing costs approximately $38,000 to identify a single patient eligible for pemigatinib. NICE estimated that adding FGFR2 as a target to the NHS panel test would incur an additional cost of £34, or £340 for each additional person identified who is FGFR2-positive, and a Taiwanese cost-effectiveness model applied a genetic testing fee of NT$30,000. Tissue sufficiency also limits yield: 27 of 107 FGFR2 rearrangement-positive participants in FIGHT-202 could not be evaluated with FoundationOne CDx because of insufficient DNA, and ESMO advises that the cost-effectiveness of next-generation sequencing be assessed at the local level. Tissue-based profiling fails in up to 26.8% of metastatic biliary tract cancers, which is one reason for plasma-based testing. Among 221 participants initiating pemigatinib, those with a prior cancer-of-unknown-primary diagnosis had higher ambulatory costs ($8,584 versus $5,308 per patient per month) and shorter median overall survival (10.2 versus 30.7 months), and the authors recommend reflexive genomic testing for cancer of unknown primary. At approval, the FDA required further validation studies before a companion diagnostic for lirafugratinib is specified in labeling.

Economic impact of diagnostic testing: cost consequences of an unresolved primary site

“CUP was associated with significantly higher prevalence of metastatic disease (100.0% vs 63.6%), per patient per month (PPPM) ambulatory HCRU (8.2 vs 5.5), and ambulatory costs ($8584 vs $5308). Medical costs averaged $13 444 vs $9881 PPPM for CUP and non-CUP, respectively (P = .066). Median OS was significantly shorter with CUP (10.2 vs 30.7 months).” (opens the source at this quote in a new tab)
“With the advent of targeted treatments for gene-altered CCA, reflexive genomic testing should be encouraged for all patients with CUP.” (opens the source at this quote in a new tab)
“Reflexive genomic testing upon CUP diagnosis may help reduce delays in identifying actionable targets and initiating appropriate targeted therapy.” (opens the source at this quote in a new tab)

Economic impact of diagnostic testing: yield of comprehensive genomic profiling

“This retrospective single-center observational study included 91 patients with BTTs who underwent CGP.” (opens the source at this quote in a new tab)
“Potentially actionable genomic alterations were identified in 21 patients (23.1%). Expert panel-based therapeutic options were identified in 15 patients (16.5%), and genomically matched therapy was introduced in 7 patients (7.7%).” (opens the source at this quote in a new tab)
“CGP revealed a heterogeneous genomic landscape across BTT subtypes and provided clinically actionable information in a limited but meaningful subset of patients. The practical utility of CGP was the greatest in selected molecular subsets, particularly iCCA.” (opens the source at this quote in a new tab)

Economic impact of diagnostic testing: guideline requirement for molecular analysis

“Molecular analysis is recommended in advanced disease considered suitable for systemic treatment [I, A]” (opens the source at this quote in a new tab)

Economic impact of diagnostic testing: cost of FGFR2 testing per eligible patient identified in Canada

“The price reduction is influenced by the cost of testing, which is estimated to be $38,000 to identify a single patient eligible for treatment with pemigatinib.” (opens the source at this quote in a new tab)

Economic impact of diagnostic testing: failure rate of tissue-based profiling

“The failure rate of tissue-biopsy profiling in metastatic biliary tract cancer is as high as 26.8%” (opens the source at this quote in a new tab)

Economic impact of diagnostic testing: companion diagnostic for lirafugratinib

“Conduct adequate analytical and clinical validation studies to support revisions to the labeling of lirafugratinib to specify the use of an FDA- authorized in vitro companion diagnostic device to accurately and reliably identify patients using blood and/or tissue samples who have FGFR2 fusions and other rearrangements and for whom lirafugratinib therapy is indicated.” (opens the source at this quote in a new tab)

Economic impact of diagnostic testing: tissue sufficiency and parallel profiling with a comprehensive panel

“Of the 107 FGFR2 rearrangement-positive patients enrolled in FIGHT-202, 27 could not be evaluated with F1CDx because of insufficient DNA.” (opens the source at this quote in a new tab)
“F1CDx offers the additional benefit of profiling multiple actionable alterations (eg, IDH1) in parallel, especially in diseases like CCA, where tumor tissue is scarce.” (opens the source at this quote in a new tab)
“F1CDx provides important options for patients with CCA; it is the first companion diagnostic approved in the United States for CCA, a devastating disease with limited treatment options but rich with actionable targets.” (opens the source at this quote in a new tab)
“Widespread adoption of testing for FGFR2 rearrangements by comprehensive genomic profiling in patients with CCA will enable more patients to be matched with targeted therapies with the goal of improving outcomes for this disease.” (opens the source at this quote in a new tab)

Economic impact of diagnostic testing: local assessment of the cost-effectiveness of next-generation sequencing

“ESMO recommends carrying out multigene NGS in patients with advanced cancers in countries where tumour-agnostic targeted therapies are accessible. Cost-effectiveness should be assessed at the local level and the decision to implement NGS should be taken accordingly.” (opens the source at this quote in a new tab)

Economic impact of diagnostic testing: cost of adding FGFR2 to the NHS England panel test

“At the first appraisal committee meeting, the clinical experts advised that FGFR2 testing is not done as part of routine clinical practice in the UK. The committee noted that the 2020/21 National Genomic Test Directory does not include FGFR2 mutation testing for people with cholangiocarcinoma.” (opens the source at this quote in a new tab)
“The prevalence of FGFR2 fusion or rearrangement is about 10% across all types of cholangiocarcinoma. So, adding FGFR2 as a target would incur an additional cost of £34, which would be applicable if pemigatinib is recommended for routine use in NHS practice. This gives a preferred cost of £340 for each additional person identified who is FGFR2-positive.” (opens the source at this quote in a new tab)