NEW YORK – Diagnostics commercialization and data analytics firm Diaceutics has seen notable declines in the number of newly diagnosed cancer patients in the month of March amid the COVID-19 pandemic.
These undiagnosed individuals are missing opportunities for treatment, and in cases where molecular testing would have been part of the standard of care, that means missed opportunities for precision care. In certain tumor types, such as lung cancer, where practice guidelines support molecular testing for multiple markers, Diaceutics' analysis shows significantly lower testing rates in March, suggesting that a substantial proportion of patients may not be getting the appropriate care.
For the most part, oncologists, patient advocacy groups, and cancer testing companies queried during the month of March and April said that every effort is being made to ensure that testing to guide precision oncology is staying on track during the pandemic. Nonetheless, it's undeniable that the pandemic has disrupted the day-to-day goings on at many healthcare facilities and labs.
Cancer centers and hospitals have stipulated rules to try to limit the number of patients coming into facilities, and oncologists are using telemedicine to check in with cancer patients who are already on treatment. Industry observers have also noted that health systems have cut back on preventive health procedures, such as mammograms, which are part of the workup for individuals with cancer. Meanwhile, it's also evident that fear of becoming infected by the SARS-CoV-2 virus is keeping people home, which means they're not coming into healthcare settings for wellness visits, or to discuss health concerns with their doctors.Â
Diaceutics recently launched a COVID-19 oncology tracker to try to quantify the impact of the pandemic on cancer diagnoses and biomarker testing for the drug and diagnostics companies it consults. The tracker draws on real-time data from labs that Diaceutics has agreements with and lab claims data from commercial and public payors. From this data, Diaceutics is able to draw insights about patients' testing experience from cancer diagnosis to receipt of advanced biomarker analysis.
To determine the cancer diagnosis rate, Diaceutics uses relevant ICD and procedures codes to identify a patient population that is then normalized to the National Cancer Institute's incidence rates within its Surveillance, Epidemiology, and End Results program. To determine the biomarker testing rates, the company compares the number of diagnosed patients against those who got biomarker testing using claims and lab network data. Â Â
The numbers Diaceutics has tracked in the last month offer a window into the impact lockdown rules and fears over SARS-CoV-2 infection may be having on the US health system's ability to diagnose new cancer patients.
The biggest impact Diaceutics has seen is within lung cancer, where the number of newly diagnosed patients from February to March dropped by 31 percent. During that same period, the number of newly diagnosed colorectal cancer patients dropped by 14 percent, new patients with acute myeloid leukemia also dropped by 14 percent, and the number of new breast cancer and ovarian cancer patients dropped by 8.4 percent and 8.6 percent, respectively.
"The numbers make a lot of sense socially with what everybody's going through at this time," said Diaceutics Chief Commercial Officer Jordan Clark. "These patients aren't going to the hospital for perhaps the cough that's been there a bit too long or the lump they have been feeling."
Diaceutics defines newly diagnosed cancer patients as those who are recorded in its database for the first time as having undergone a biopsy and surgical pathology testing. In order to be diagnosed, patients must have these types of assessments, and Diaceutics tracks those codes as the tests are performed on a weekly and monthly basis.
The number of newly diagnosed patients are reflective of all the downstream testing, including molecular testing, and treatment that's not happening. When it comes to molecular testing rates, the biggest drops Diaceutics has seen is for KRAS, BRAF, and EGFR mutation analyses for lung cancer patients, which in March were down 7 percent, 11 percent, and 13 percent, respectively, compared to the prior month.
Cancer centers are increasingly testing non-small cell lung cancer patients for KRAS mutations to try to get them on a clinical trial studying KRAS inhibitors. The FDA has approved dabrafenib and trametinib (Novartis' Tafinlar and Mekinist) for NSCLC patients with BRAF V600E mutations and has approved multiple EGFR inhibitors for individuals with exon 19 deletions or exon 21 (L858R) substitutions.
With regard to EGFR biomarkers, specifically, Diaceutics estimates that the reduction in mutation testing rates translate to nearly 4,000 fewer tests being performed, just in March alone.
Clark suspects that Diaceutics is seeing the biggest impact in lung cancer diagnosis and testing rates during the pandemic because COVID-19 is a respiratory disease. Perhaps the symptoms that patients would have gone in to see the doctor for, they are mistaking for COVID-19, or they may just be more reluctant to go see the doctor for their cough and risk SARS-CoV-2 infection, he opined. A study presented today at the American Association for Cancer Research's Virtual Annual Meeting found that thoracic cancer patients had a 34.6 percent mortality rate due to COVID-19.Â
In AML, Diaceutics tracked a 12 percent decline in FLT3 mutation testing, and an 11 percent and 12 percent drop in IDH1 and IDH2 mutation testing, respectively. The FDA has approved drugs for AML patients in these biomarker-defined subgroups. In CRC, precision oncology treatments are available for those with BRAF mutations, microsatellite instability or mismatch repair deficiency, and RAS mutations, and testing rates for these biomarkers from February to March decreased by 9 percent, 8 percent, and 6 percent, respectively.
Testing in these cancer categories may not be impacted as dramatically as NSCLC for a variety of reasons. For example, by the time AML patients are diagnosed, they tend to be very sick and are immediately hospitalized, at which point the biomarker workups are done to quickly get them on therapy. These types of patients may be more likely to come into the healthcare setting despite the pandemic. In CRC, patients have other options and may not be as reliant on biomarker testing to get on treatment. (In breast and ovarian cancer, further analysis is ongoing to assess the impact on biomarker testing, which Diaceutics hopes to make available soon.)
While there is a small degree of variation in testing rates from month to month, Clark said, the trend is consistent across the different biomarker testing categories in terms of a more "pronounced" drop in the month of March. He is expecting the diagnosis and testing rates to continue going down even more in April, since during the entire month most people throughout the US were ordered to stay at home.
This, in turn, will undoubtedly impact the revenues of labs, diagnostics companies, and drug developers. "These are pretty big numbers for pharmaceutical companies and laboratories to be leaking," Clark said.
Diaceutics reached out to some of its lab and pathology partners to ask what kind of impact they are seeing on cancer diagnosis and related biomarker testing. A pathologist at one community hospital estimated a 25 percent drop in oncology testing volumes. Another pathologist at an academic medical center said specimen volume was down by 70 percent for cancer and non-cancerous cases, and further recounted that since fewer surgeries were being performed, "biomarker testing is subsequently severely decreased."
Lab professionals also described to Diaceutics the safety measures and staffing adjustments they've had to make during the pandemic. "We are keeping only 33 percent [to] 40 percent MD [or] PhD staffing on-site at the lab," one expert at a commercial reference lab said. "There has also been decreased staffing at the technologist level and layoffs of non-key personnel."
Resilience amid a pandemic
The full financial impact of the public health crisis on life sciences companies may take some time to realize and may shift for the better or worse depending on the trajectory of the pandemic in the coming months. Roche, as a leading developer of precision oncology drugs and diagnostics, had what CEO Severin Schwan described as a "resilient" first quarter. At the same time, he acknowledged that the company had definitely been impacted by the pandemic and at the start of the year, executives could not have guessed which segments of the business would end up being successful during the first quarter.
The company as a whole reported CHF 15.14 billion ($15.65 billion) in sales in Q1, a 7 percent increase from CHF 14.83 billion in Q1 2019. In the coming months, the company is expecting "some volatility" in its business, but for the time being Schwan confirmed the 2020 financial outlook and noted that during Q1 the launch of new molecular entities and pivotal data readouts from ongoing studies were "largely on track."
Schwan told investment analysts, however, to watch out for potential delays to starting new patients on clinical trials, since healthcare centers are focused on COVID-19. The company is expecting such delays to impact studies for chronic disease drugs, more so than oncology. "We do see during this time of a pandemic that patients have a tendency to want to stay on whatever therapy they're already on. In some cases that can lead to delays in new patient starts, including innovative new therapies," said Bill Anderson, CEO of Roche's pharmaceutical business, which during Q1 contributed CHF 12.26 billion, marking a 7 percent year over year growth in sales.
Clinical studies in oncology will likely be less impacted, Anderson predicted, because "unfortunately, cancer doesn't take note of pandemics, so these patients' … needs remain high and we are continuing to enroll studies in cancer."
Meanwhile, the company's diagnostics business, which contributed CHF 2.88 billion in Q1, marking a 5 percent year-over-year increase, saw different mix in terms of the segments that fared well during the pandemic. Molecular diagnostics testing grew 29 percent during the quarter, driven in large part by greater point-of-care flu and COVID-19 testing. The company's centralized testing segment was heavily impacted by the lockdown due to COVID-19 in China. Tissue-based testing, which comprises testing for guiding cancer therapy, grew 12 percent, and saw no impact from COVID-19, according to company executives. In particular, companion diagnostics sales grew by 30 percent.
Roche owns Foundation Medicine, the leading provider of tissue-based next-generation sequencing for informing cancer treatment, but the company did not break out the company's revenues.
In a recent interview, Dave Fabrizio, VP of translational strategy at Foundation Medicine, said the company has implemented best practices during the pandemic to manage on-site staffing in order to keep test volume "as high as possible" and turnaround times "as low as possible." As a result of those best practices, Fabrizio said Foundation hasn't seen "any impact on turnaround time or volume."
Even though its Q1 financials weren't too negatively impacted by COVID-19, Roche has modeled how its business may be impacted in the future based on how the pandemic plays out. In one scenario, after the first wave of COVID-19 cases, Roche expects its business might be affected by intermittent societal restrictions if there is an uptick in the number of cases throughout the year. In another scenario, societies will ease restrictions, accepting that there will be a medium-to-low level of positive cases but not so many that it will overwhelm intensive care units. This second situation will get people back to work faster, though the company is preparing for both possibilities.
Impact not yet in focus
Although Roche for one is not expecting its clinical trials in cancer to be much impacted, it may be several more months before the consequences of the pandemic on new study starts becomes fully apparent. DeciBio Consulting, a life sciences consulting and market research firm, recently queried clinicaltrials.gov for the number of trials that had changed their status from "not yet recruiting" to "recruiting" in the first three months of the year in 2018, 2019, and 2020.
Using specific search terms, Colin Enderlein, a Senior Associate at DeciBio, identified 2,800 immuno-oncology biomarker studies and found that 25 percent of trials made this status change on clinicaltrials.gov in Q1 2018 over an average of 4.3 months. Similarly, in Q1 2019, 8 percent of trials converted from "not yet recruiting" to "recruiting" status over an average of 4.3 months. In Q1 this year, 8 percent of trials made the status conversion, taking on average less than a month to make this change on the site.
To Enderlein, this indicated that no appreciable deviation from the prior year could yet be detected based on the public database. Of note, nine out of the 13 trials that converted in Q1 2020 did so prior to mid-March, when most national stay-at-home orders went into effect. Since it historically has taken around four months for trials to start recruiting, Enderlein expects that any discrepancies in this year's data compared to past years will become apparent by June or July. (At the time of his analysis, as a benchmark, 65 percent of Q1 2020 studies were in "not yet recruiting" mode.) This status conversion will be important to track not only as an indicator of how the pandemic is impacting biomarker-guided cancer trials, but the conversion "is going to be one of the big signs that trials are actually getting back on track," he said.
One of the reasons the true effect of the pandemic may not be currently captured on clinicaltrials.gov may be because updating the status of the studies on the site may not be a priority right now for study investigators. Nonetheless, Enderlein predicted that biomarker cancer studies may be particularly impacted because during the public health crisis more resources are being shifted at reference labs and CROs toward COVID-19 research. "They're all preoccupied and basically the resources are being refocused on doing COVID research," he said
Diaceutics said it will also keep a close watch on the diagnosis and testing numbers in its database. "It's going to be interesting over the next two-to-three months to see what these numbers do," Clark agreed, noting that how things shake out may depend a lot on how the return to normalcy is managed by the various US states and how people respond to that.
Even if some states loosen stay-at-home restrictions and open up businesses, Clark said there is a very real possibility that some people may not be willing to return to their normal way of life. In that scenario, these cancer diagnosis and biomarker testing rates may take longer to return to pre-pandemic levels.Â
Some places in the US are said to be at peak infection rates, but even so, Clark observed that means there are still many more patients that will need to come into the hospital for care before infection rates go down to zero. "The hospitals are still going to be really busy treating those patients, and there are still going to be a lot of infectious patients going into those hospitals, which people are going to be wary of," he said. "I don't think we can get a rush back to normal with everybody going to visit their general practitioner and family doctor."