NEW YORK – Diagnostic firm Invitae and drug giant Pfizer recently launched a program to expand the availability of BRCA1/2 testing among breast cancer patients in six countries with otherwise limited access.
While the program may improve genetic testing access for inherited cancer risk, it still must operate within these countries' existing healthcare infrastructure. As such, patients may still lack access to the downstream screening and treatment interventions that may be indicated based on their genetic test results.
San Francisco-based testing firm Invitae, with its stated core mission to "make medical genetics affordable and accessible for everyone," has launched numerous no-cost testing programs with other drugmakers and organizations, but this is the first one with a global focus. Within the BRCA Care program, Invitae will provide testing on its BRCA1/2 STAT panel and Pfizer will pay for the testing that will be available to patients in 17 regions, beginning with a select six countries located in the Middle East and Asia Pacific.
In order to be eligible for the free testing program, patients must have HER2-negative, locally advanced or metastatic breast cancer and live in Hong Kong, Oman, Qatar, Saudi Arabia, Taiwan, and the United Arab Emirates.
"The whole idea is that there's this logjam or barrier to widespread adoption of what we think is very valuable information," Invitae Chief Medical Officer Robert Nussbaum said in an interview. "We're trying to break up that logjam, and some of that we may do on our own, and some of that we may do with sponsored testing."
Invitae has successfully launched low- or no-cost germline variant testing programs, such as its US- and Canada-based Detect Hereditary Pancreatic Cancer and Detect Hereditary Prostate Cancer programs, and has gleaned valuable information while expanding patient access to testing. But the far-reaching international focus is new for the company.
"Our general approach is that we want to make genetic information available and accessible to everybody who can benefit from it on the globe," Nussbaum said. "We really wanted to start an international program," he added, noting that the partnership with a pharmaceutical firm like Pfizer, with a global presence, allows just that. The program will also benefit Pfizer by identifying advanced breast cancer patients with BRCA1/2 mutations who may be eligible to receive its PARP inhibitor talazoparib (Talzenna).
In addition to providing no-cost BRCA1/2 mutation testing to eligible patients, Invitae and Pfizer are also offering patients the chance to get tested for other cancer risk mutations on one of Invitae's larger, multi-gene panels, which will also be free of charge if ordered within 90 days of the first test. Though patients do not need to have received specific BRCA1/2 results to take advantage of the expanded testing option, Nussbaum explained that the larger panels may be informative in cases where patients test negative for BRCA1/2 mutations, but their clinicians suspect, based on family history and other clinical factors, that they still may be at risk for a hereditary cancer syndrome. The lab won't require a new sample for this additional analysis.
Importantly, since a positive result for a patient also has implications for the inherited cancer risk of his or her blood relatives, the BRCA Care program guarantees free cascade testing for family members. Specifically, the program will provide free variant testing to any number of family members of a patient who tests positive for a pathogenic or likely pathogenic variant if ordered within 90 days of the original patient's test.
The free cascade testing aspect of the program is the feature that most excites Nussbaum. "I'm very curious as to whether there are cultural issues that either mitigate against or promote cascade testing in different societies," he said, explaining that Invitae has launched no-cost, family follow-up testing alongside a number of its diagnostic or proactive testing programs in the US and Canada already, but the uptake remains low. "It would be fascinating if the uptake of family variant testing [in these regions] propagates out from the original family."
In exchange for the free tests, patients and any family members who undergo germline testing through the BRCA Care program will agree to share their deidentified information with Pfizer, which the companies hope will inform further research. Specifically, according to a Pfizer spokesperson, the deidentified patient information will allow the company to "better understand trends in BRCA testing" to improve future educational initiatives.
Though Nussbaum acknowledged that he could not speak directly to the ways in which Pfizer would study patients' deidentified information gleaned through the program — such as detected genetic variants, disease symptoms, and other relevant health information — he offered examples of how the patients' test results could potentially prove valuable.
"Everything we know about hereditary breast cancer is derived from people of European extraction," he said. "I'm very interested in identifying other disease-causing changes that have not been seen before in people who don't come from that region of the world." And, as for information gleaned from larger test panels, he added, "We're very interested in whether there's any sort of non-classical genes that turn out to be important contributors to breast cancer that have not been recognized before."
Testing access, selected regions
By improving access to germline BRCA1/2 testing specifically for patients who have already been diagnosed with advanced breast cancer, the BRCA Care program has the potential to shape these patients' treatment paths.
Specifically, given that patients with advanced breast cancer harboring germline BRCA1 or BRCA2 mutations may be eligible for targeted treatment with a PARP inhibitor, the National Comprehensive Cancer Network (NCCN) recommends that all patients diagnosed with recurrent or metastatic breast cancer undergo germline BRCA1/2 testing. On the basis of these guidelines, insurers in many countries including the US will usually cover germline BRCA1/2 testing for patients who fit these criteria.
Although access disparities in the US persist, according to Sue Friedman, the executive director of the patient advocacy group Facing Our Risk of Cancer Empowered (FORCE), in recent years test affordability has improved domestically. Even for patients without insurance, "most of the major labs that do genetic testing for inherited cancer have options for low-cost testing that bring [the price] down to under $500," she said. For example, in the US, Invitae offers a $250 self-pay option for uninsured patients.
"I'm not saying that's nothing," Friedman said. "But it's not the thousands of dollars it used to cost."
Zoom out globally, however, and the same does not necessarily hold true. Policies impacting access to hereditary cancer mutation testing vary from country to country, making it challenging to compare data on germline BRCA1/2 testing access and costs between regions. Pfizer, however, analyzed access barriers internationally, according to the company spokesperson, and decided to launch BRCA Care in six countries it pinpointed as having a challenging reimbursement environment, high out-of-pocket costs, and slow turnaround time for test results.
Treatment implications for patients, relatives
While BRCA Care's stated goal is to improve patient access to testing — and, accordingly, empower them with the information needed to inform their best course of treatment — the program has the potential to directly benefit the pharmaceutical company that's sponsoring it, too.
Patients qualify for no-charge testing through the program only if they have been diagnosed with locally advanced or metastatic, HER2-negative breast cancer. If these patients are found to be positive for pathogenic germline BRCA1/2 mutations, they may also become eligible for Pfizer's PARP inhibitor talazoparib.
The US Food and Drug Administration approved talazoparib in 2018 for patients with locally advanced or metastatic HER2-negative breast cancer who carry germline BRCA1 or BRCA2 mutations. And while the FDA has cleared for marketing Myriad Genetics' BRCA CDx as talazoparib's companion diagnostic, in the real world, lab-developed tests without the agency's approval are readily used to test cancer patients for treatment planning.
Still, drugmakers may be hesitant in the US to support the use of tests without FDA approval alongside their drugs, but this is not an issue outside the US. As such, Invitae's free BRCA1 and BRCA2 STAT tests are also serving the purpose of identifying patients who may be eligible for treatment with Pfizer's drug and competing PARP inhibitors approved for BRCA1/2-mutated advanced breast cancer, such as olaparib (Merck/AstraZeneca's Lynparza). But because of Pfizer's affiliation with the free testing program, the drugmaker is undoubtedly hoping that this will bolster sales of its drug.
While talazoparib can be given as a first-line option in this biomarker-defined, metastatic setting, olaparib's label stipulates that advanced breast cancer patients must have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting first. That said, olaparib currently has a bigger market share than talazoparib, in part because the drug has been available on the market longer and has been approved in the US and other markets for multiple indications, including ovarian, pancreatic, and prostate cancers.
In 2019, AstraZeneca reported $1.19 billion in olaparib sales. Pfizer, on the other hand, did not break out talazoparib's revenues as it does for its top-earning oncology products in a press release detailing its 2019 financial performance. Meanwhile, Pfizer is actively working on expanding talazoparib's use in other cancer indications, both alone and in combination with avelumab (Pfizer/ EMD Serono's Bavencio). In addition to pursuing other uses for the drug, improving its adoption among breast cancer patients in new geographic regions may also help grow worldwide sales. Â
Importantly, while Pfizer said that its aim in sponsoring the BRCA Care program is to help inform patients' treatment plans through improving access to genetic testing, the company stopped short of confirming that expanding the market for talazoparib directly incentivized its involvement. Toward the bottom of the BRCA Care website, an italicized statement explicitly reads, "Healthcare professionals and patients who participate in this program have no obligation to recommend, purchase, order, prescribe, promote, administer, use or support any other products or services from Invitae or from Pfizer."
Testing versus treatment access
In the US, talazoparib received accelerated approval on the basis of a clinical trial in which patients receiving Pfizer's drug lived an average of 8.6 months without their cancer progressing versus 5.6 months for patients treated with standard-of-care chemotherapy. The objective response rates with talazoparib versus chemo were 62.6 percent and 27.2 percent, respectively, and patient-reported outcomes favored talazoparib.
However, patients can't benefit from a drug they can't afford to receive. Pfizer may be covering the cost of BRCA testing, but it is not guaranteeing coverage for the treatments indicated by testing. While drug prices and patients' out-of-pocket costs may differ internationally according to countries' specific payor systems, the wholesale acquisition cost for talazoparib in the US is $15,309 per month for the 1 mg recommended starting dose. Pfizer does have various patient assistance programs, but there is no guarantee that patients who test positive for a germline BRCA mutation within BRCA Care will qualify for payment assistance or be able to pay for talazoparib out of pocket.
Beyond the immediate treatment implications for breast cancer patients, the availability and cost of downstream interventions, such as more frequent screening via imaging or preventive surgeries, may also be an issue for patients and their family members. For example, while coverage, cost, and availability differ internationally, Nussbaum acknowledged that in the US, even though the National Comprehensive Cancer Network recommends breast MRIs as the preferred screening method for patients who are deemed high-risk on the basis of germline BRCA1/2 mutations, insurance coverage for breast MRIs is "all over the map." Prophylactic mastectomies for high-risk patients, moreover, may be covered by private insurers, but not under Medicare.
"One of the biggest needs that we see is access to resources and financial assistance to pay for what comes next after testing," said FORCE's Friedman. "Access to preventative options vary, but here in the US, one of the issues we are seeing is that women are having to pay quite a bit out of pocket for breast MRIs or preventative surgery. … That's challenging because the benefits of knowing you're high-risk are being able to take risk-reducing measures, and there are real gaps in that access in the US as well as globally."
Importance of genetic counseling
Though Friedman declined to comment directly on Pfizer and Invitae's BRCA Care program, she emphasized that access to genetic counseling is another key consideration within such no-cost testing programs. The NCCN recommends that patients who undergo testing for hereditary cancer mutations speak with a certified genetic counselor both before and after testing. Counseling can ensure that patients understand what to expect in agreeing to get tested, and ultimately what their test results mean for treatment and prevention.
"Any program that addresses aspects of barriers to genetic testing is helpful," she said. "But I do think it's also important to make sure that we're providing resources and access to genetic counseling as well."
Although the consent form that patients must sign prior to receiving the no-cost tests includes a recommendation that patients "consult with a genetic counselor or healthcare provider" before and after testing, the BRCA Care program itself does not guarantee that patients or their family members will have access to this genetic counseling. This, Nussbaum acknowledged, would be a valuable service, but Invitae does not yet have the infrastructure to offer genetic counseling on a patient-by-patient basis globally. The company is developing international genetic counseling services, but because of the nuanced cultural differences unique to each country, as well as differences in certification standards for genetic counselors — if such standards exist at all — the program will take time to establish.
The company is starting small. "We think that it's really important for genetic counselors to be embedded in the society and [know] the medical norms where they're working and where their patients are," he explained. In the US and Canada, Invitae does offer genetic counseling to patients, which it does through telehealth appointments and patient-specific follow-up summary letters.
BRCA Care does provide "clinical consult services" to providers, however. Within the service, doctors can contact Invitae's board-certified genetic counselors in case they want to discuss the clinical implications of test results.
"The sort of information that you get from the clinical consult service is in a sense generic," Nussbaum acknowledged. "It's not meant to be specific to a particular patient." Genetic counseling, on the other hand, differs in that it "digs much more into the particular patient situation and their particular patient and personal family history."
As no-cost testing through the BRCA Care program reaches patients in distant areas of the globe, the question as to whether patients will be able to access adequate counseling services to parse the implications of their results — and to afford the treatments and interventions that these results may dictate — remains unknown. When asked whether he thinks it is ethical to let people know their BRCA status if they may not have the means to access what comes next, Nussbaum admitted, "it's a tough question."
"Each person's results and recommendations can be so different based on their situation and circumstances," he said, adding that a medical system that would withhold or limit access to potentially lifesaving interventions is "broken and unjust."