Most oncologists feel that genomic testing is useful, but not all would order a test for their patients. The experts at ACT Genomics tell us more.
The advent of NGS to improve precision cancer care
Up-to-date, genetic and genomic testing in cancer has transformed cancer management. Next-generation sequencing (NGS)-based multigene panels, among all genomic analytical platforms, are the most remarkable scientific advance in precision oncology. By stratifying patients and administering the right treatment at the right time, NGS has revolutionised how we enhance treatment response and hold the promise of turning cancer into a manageable chronic disease (Figure 1).
As more targeted anti-cancer agents and immuno-oncologic drugs are approved and introduced in Asia-Pacific, cancer patients and doctors in the region are now becoming more aware of the use of NGS-based molecular profiling. Cancer specialists, in particular, medical oncologists are deploying NGS multigene panels to identify potential cancer biomarkers for diagnosis and prognosis purposes.
Multiple cases have shown considerable improvement after actionable genetic mutations were found and the patients matched with targeted therapies. Madam C is an ovarian cancer patient in Singapore, who went through 12 courses of chemotherapy in a span of three years. However, the cancer persisted and further spread to the cervix. Using NGS-based genomic profiling, her doctor identified a rare mutation of the RAD51C gene in the cancer, and administered a targeted drug in accordance to such a specific mutation. With this therapeutic intervention, Madam C’s cancer lesions disappeared within a week. This is a real-world case that inspires both doctors and patients in the era of precision medicine.
However, is Madam C an exceptional case that happened to be treated in Singapore, one of the most advanced Asian countries? Or does she represent a subgroup of patients that benefited from a precision drug administered by an experienced oncologist? What about the practice and perception of the vast majority of doctors in the Asia-Pacific? How are oncologists adopting and deploying these genomic tests in their daily practice? When in the course of disease are they using such tests? How confident are doctors in interpreting NGS results, especially for less common mutations, and integrating them into clinical decisions? What are the challenges that hinder doctors from using such technology? These are the questions to be answered.
Oncologists’ views on NGS panel testing
To understand and gain insight into oncologists’ views on NGS testing in Asia-Pacific, 87 cancer specialists (mainly medical, hematologic and surgical oncologists, 79.3% percent) from Asia-Pacific countries (mainly Taiwan, Thailand, Philippines, and China, 77 percent) were surveyed face-to-face between February 2018 and October 2018. The survey instrument was initially developed by Medscape 2016, but its content has been adjusted to reflect the regional practice in Asia. To analyse the variations in concept and behavior among all surveyed oncologists, respondents were categorised accordingly. Group A (51.8 percent) were doctors who have used NGS at some point and Group B (48.2 percent) were those who have not used NGS. They were compared on two dimensions: 1) Their perception of using NGS multigene panel testing, and 2) their practice of NGS multigene panel testing.
Perception of the importance and usefulness of NGS multigene panel testing
All respondents agreed that NGS testing in the field of oncology is either extremely important or very important (79 percent, Figure 2). Yet, about one third of the interviewees find such technology still at its infancy, and may need another 5 to 10 years to be applicable in the clinical setting.
For Group B respondents who have never ordered a genomic test for their patients, higher numbers (85.7 percent in Group B versus 68.8 percent in Group A) were mainly concerned with financial toxicity issues, such as the cost-effectiveness of genomic testing, and whether both genomic tests and subsequent therapies in unapproved indications are covered by either government or private insurance schemes.
It was not surprising that Group A seemed more in favour of NGS testing as compared to Group B (73.3 percent versus 57.1 percent). Despite their reservations, 65.5 percent of all surveyed oncologists felt that genomic testing is clearly useful today. The majority (90 percent) of those who do not feel so indicated that such testing would be useful in the years to come (Figure 3).
NGS use will move beyond research settings even in the absence of robust evidence (59.7 percent), which implies the potential of applying NGS to current clinical practice. There is a strong overall consensus (90 percent) that it is critical to familiarise oncologic practitioners with scientific education before genomic testing can be widely used.
However, two thirds of interviewees expressed that the clinical utility of ‘routine’ multigene panel testing is unclear and thus currently cost-ineffective to support its widespread use. This might be a result of unclear guidelines on how to apply NGS testing, lack of regulatory endorsement, and whether insurance policies can reimburse off-label drug use.
Regarding clinical concerns with genomic testing, cost-effectiveness of the testing emerged again as the top concern with 40.2 percent (Figure 4) stating it as not being cost-effective. This further illustrates that the diffusion of such technology is mainly crippled by financial burden in its deployment and clinical efficacy in the molecular findings. This obstacle must be overcome before doctors can adopt this technology on a widespread basis.
The second concern for oncologists in prescribing NGS testing is whether the genetic alterations in the NGS report are truly clinically actionable, e.g., whether these findings are backed with sufficient evidence, indicating that approved therapies will work for the vast majority of mutations (22.9 percent). Far too often, test results do not lead to any changes in patient management.
The availability of cancer tissue for NGS testing is the third major concern that deters oncologists from adopting this technology (21.8 percent). Indeed, the quality of cancer tissue, e.g., sometimes the way it should be processed and stored, is the most critical factor affecting the adoption of NGS technology, especially in countries where surgeons (who obtain the specimen) and pathologists (who manage the tissue fixation) are not aware of the sample requirements for NGS genomic testing.
Practice of NGS multigene panel
Younger oncologists (between age 31 and 50 years), especially those with more than 10 years of experience, are generally more fervent in bringing this NGS platform to their clinical practice. In fact, one quarter of Group A ordered the test at the time of the survey.
On the other hand, most respondents in Group B are accustomed to using single gene based molecular assays (such as immunohistochemistry, IHC or fluorescence in situ hybridisation, FISH) in their daily practice. Such conventional diagnostic tests have been the standard of diagnostics for many years, and are clearly defined in the clinical guidelines for cancer treatment. Often, they are also heavily subsidised by public agencies or reimbursed by private insurance policies.
Interestingly, the survey shows Group B’s institutions fail to provide relevant molecular education/training, not to mention the setup of molecular tumour boards. On the contrary, Group A doctors are well supported by their healthcare organisations to provide scientific guidance. This highlights that the adoption of this technology has significant relation to the level of understanding of the oncologists, and their ability to decipher the lengthy technical reports that often contain complex genetic findings.
Regarding the timing to adopt multigene panel testing, both groups indicated similarly: when standard of care is no longer viable (63.1 percent), when conducting research (58.6 percent), and when there is metastatic progression (49.4 percent) (Figure 5). The survey also showed, compared to Group B, Group A was more aggressive in using NGS panels as soon as there was progression in their patients’ disease.
When surveyed for the primary motive for using genomic testing, oncologists overwhelmingly chose to order such tests to guide their clinical decisions (77.8 percent, Figure 6). This is despite the fact that a substantial portion in this group felt that these tests provide few clinically actionable information. Strikingly, only two percent of oncologists said they ordered genomic tests to guide their patients to a clinical trial. This finding is much lower than Medscape’s survey results for U.S. oncologists (16 percent for the same question). The survey indicates the reality in Asia-Pacific where clinical trials are not as readily available, so physicians are not able to enroll their patients to trials for unapproved drugs suggested by the genomic findings.
In general, surveyed oncologists in both groups showed substantial confidence in using NGS test results to guide their treatment decisions. Specifically, Group A demonstrated higher confidence in guiding their patients along the course of disease and counseling them on the genetic testing results.
Given the variety of commercial multigene panels available and no clear guidance on what test to be ordered, majority (58.6 percent) would turn to National Comprehensive Cancer Network (NCCN) guidelines or society guidelines, whereas 31 percent turned to scientific studies (Figure 7). Interestingly, Group A was more confident in making treatment decisions by searching and studying references from scientific studies. This may indicate that the variation in NGS adoption might be due to a higher level of knowledge and academic inquiry in Group A.
The emergence and great potential of NGS herald a new era in genetic diagnostics. Many oncologists surveyed believe that NGS panel testing holds promise as an advance for cancer management and is extremely important to the field of oncology. However, it currently underperforms in terms of clinical use, especially in Asia-Pacific. The survey has captured the reality that the NGS technology does pose challenges to clinicians and patients, both at the technical level and in terms of clinical efficacy of the testing, the quality control of the specimens, as well as the interpretation of the results and the curation of the database to be used.
In order for NGS genetic testing to be widely adopted, several steps need to be in place. The survey shows the most critical factor to be educating both the medical community and the public, before advocating for broad genomic testing. Through education, cancer specialists can be more confident in knowing when to use NGS testing and how to interpret testing results to guide therapy decisions.
As for the public such as patients and caregivers, educating them will see to the increase of their requests for the test. This will generate more data on clinical outcomes, and eventually help build a cost-effective model for health authorities and private payers such as insurance companies to review and revise their reimbursement policies and pricing strategies. The ultimate goal is reducing the financial burden of NGS testing substantially so that cancer patients in need are able to benefit from NGS test results to better manage their disease, just like Madam C.
Dr Allen Lai is the senior vice president at ACT Genomics Taiwan, and regional managing director at ACT Genomics Singapore.
Tung Kai Che is the medical science liaison at ACT Genomics Taiwan.
Seo Tho Wee Siang is the sales director at ACT Genomics Singapore.