Within the past decade, there has been a surge in terms such as value-based care, patient-centered care, shared decision-making, and more at the macro level of health care delivery in the US.
THE PAST DECADE has seen a surge in terms such as value-based care (VBC), patient-centered care, shared decision-making, patient-reported outcome measures, and precision medicine (PM) at the macro level of health care delivery in the US. At both micro and macro levels, the most rapid strides have been observed and validated in the field of cancer from an understanding of the complex interaction of epigenetics, environmental factors, and social determinants of health.1 The comprehensive analysis of the Human Genome Project2 has helped us recognize cancer as a complex set of diseases, understand the possibilities of targeted treatment options, and identify germline mutations that indicate patients at high risk.
However, the simple fact remains that nearly 34% of cancer deaths are preventable, according to the disparity report published by the American Association for Cancer Research in 2020.3 This report shows that our health care system functions in a compartmentalized approach. The only way to break silos and compartments and provide value-based, patient-centered cancer care (PCCC) with a personalized approach is to amalgamate all these factors, resulting in an ecosystem with the patient at the center. The summary of factors creating this chasm is reflected in the FIGURE.3
Without the development of sequencing techniques, bioinformatics, and PM, accessibility will continue to lag because benefits will not be available universally. Further challenges include integration into practice guidelines, lack of consensus and standardization between tests, payer coverage of testing, lack of universality of panels, discordance between minimum number of mutational analyses for testing, and lengthy turnaround time for results.
I came across a very challenging situation in 2017 when a dear friend reached out to me in a panic when his son was diagnosed with stage IV non–small cell lung cancer (NSCLC) while pursuing his doctorate in economics in the United Kingdom (UK). We built an ecosystem around this patient that included patient advocacy, family support, an international team of oncologists, and philanthropy efforts by the pharmaceutical industry (ie, an all-inclusive approach).
A 27-year-old student from India was pursuing a doctoral degree in economics in the UK. He developed progressive cough, weight loss, and shortness of breath in April 2017. He visited his general practitioner, who decided to treat him with antibiotics (azithromycin). He continued to lose weight. His chest radiograph revealed bilateral nodular lesions and a large 3.5 × 4-cm cavitary lesion in the right lung. Due to his nationality and ethnicity, he was presumed to have pulmonary tuberculosis and was treated with antituberculosis treatment for several weeks. His condition worsened. Within 2 months, he developed hemoptysis and orthopnea. He was hospitalized in June 2017. A PET/CT scan in June 2017 revealed a fluorodeoxyglucose (FDG)-avid; multiple FDG-avid bilateral parenchymal lung nodules; bilateral mediastinal, hilar, and right supraclavicular nodes; and an FDG-avid lesion in the right adrenal gland suggestive of metastatic disease. His histopathology revealed adenocarcinoma of the lung. His initial biomarker assay for cancer panel included EGFR, BRAF, TP53, PTEN, PIK3CA, PDGFRA, NRAS, and KRAS. None of the test results were indicative of actionable mutation.
Given his worsening condition, the patient was airlifted to India to join his parents. He had a diagnosis of terminal lung cancer and possible referral for comfort and hospice care. At this juncture, his family reached out to Kashyap Patel, MD, at Carolina Blood and Cancer Care in Rock Hill, South Carolina, for remote consultation. Meanwhile, they had consulted a local oncologist in India who decided to administer 1 cycle of pemetrexed, carboplatin, and bevacizumab (Avastin), with intent to add immunotherapy.
I recommended additional biomarker testing and PD-L1 testing. Results revealed an ALK mutation and a PD-L1 status of greater than 50%. I recommended starting with alectinib (Alecensa) in August 2017.
Within 4 weeks of initiating treatment with alectinib, his performance status improved and he started walking with ambulatory oxygen. After 8 weeks of treatment, the patient started walking 1 mile daily and resumed his studies remotely. His performance status improved.
His follow-up PET/CT scan in January 2018 revealed near-complete resolution of all liver metastases and adrenal metastases. His lung lesions also resolved.
In December 2018, the patient completed the thesis for his doctoral degree and got married. In March 2019, his scans confirmed no evidence of disease. He continued alectinib for another year until summer 2020. He then developed multiorgan failure and was hospitalized for several days at a local hospital in India. He had evidence of cytokine release syndrome likely from acute COVID-19. Results from his restaging studies indicated progression, including pericardial space, adrenal, and brain metastasis as well as multiple progressive liver metastases. His repeat biopsy results revealed the same molecular profile.
In the hospital, he received high-dose corticosteroids and appropriate anti–COVID-19 measures. He received whole brain radiation and was placed on brigatinib (Alunbrig) at an FDA-approved dosing schedule. Within 3 months, his follow-up brain MRI revealed near-complete resolution of all lesions and his liver lesions also responded. He completed his doctorate and is now a visiting faculty member in the UK.
PM is “an approach to disease prevention and treatment to maximize effectiveness by considering individual variability in genes, environment, and lifestyle,” according to the Precision Medicine Initiative Working Group.4 The goal of PM is to advance medical and scientific discoveries to offer more tailored, precise, and accurate health interventions and maximize health benefits for patients.5,6
Despite the evolution of multiple diagnostic modalities, PM has failed to benefit hundreds of thousands of patients due to the complexity of health care delivery. This case report reflects how an ethnic and national bias could have resulted in preventable death. This patient was presumed to have tuberculosis, which resulted in significant delay to the point that he was sent back to India to face comfort and hospice care. The second mistake was not doing comprehensive genomic profiling.
Gierman et al reported a study of 1203 patients with advanced NSCLC treated in a community setting in 2017 and 2018, where only 22% of patients underwent genotyping for all 4 National Comprehensive Cancer Network–recommended genes, with testing rates for individual genes ranging from 29% (BRAF) to 54% (EGFR).7 Findings from this study also revealed that only 45% of patients who may have qualified for FDA-approved targeted therapy had evidence of receiving targeted therapy. Furthermore, 37% of patients with a mutation in EGFR or ALK and no evidence of progression on the corresponding tyrosine kinase inhibitor received an immuno-oncology (IO) agent, although most of these patients were known to have the targeted alteration at the time of IO agent initiation.
In patients with coexpression of PDL1 and other driver mutations (in genes such as EGFR), outcomes with IO agents have been disappointing.8 KEYNOTE-024 (NCT02142738) and KEYNOTE-021 (NCT02039674) excluded patients with sensitizing mutations in the EGFR or ALK gene.9,10 The only study of immune checkpoint inhibitor (ICI) that included patients with EGFR mutations and PD-L1 expression was stopped prematurely because of lack of efficacy.8 It is reasonable to conclude there is a lack of evidence related to clinical benefit from ICIs as a first-line treatment in patients with EGFR-mutated metastatic NSCLC. Turnaround for PD-L1 testing is quick, but it may take longer to identify other driver mutations.
In summary, the advantages of PCCC, PM, VBC, and personalized medicine will only translate to extension of benefits to all patients if payers, providers, and laboratories break silos and engage in building an ecosystem around the patient. This will save lives, improve outcomes, and transform health care.
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