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JCO Precis Oncol
JCO Precis Oncol
po
PO
JCO Precision Oncology
2473-4284
Wolters Kluwer Health

38935894
PO.24.00092
10.1200/PO.24.00092
00153
ORIGINAL REPORTS
Precision Medicine
Clinical Utility of Tumor Next-Generation Sequencing Panel Testing to Inform Treatment Decisions for Patients With Advanced Solid Tumors in a Tertiary Care Center
https://orcid.org/0000-0003-2099-0542
Bogdan Lucia MD 1
Saleh Ramy R. MD, MSc 2
Avery Lisa PhD 3
Del Rossi Samanta BSc 3
https://orcid.org/0000-0002-8764-1091
Yu Celeste BSc, MSc 3
https://orcid.org/0000-0002-6771-2999
Bedard Philippe L. MD 3
1 Division of Medical Oncology, Department of Medicine, University of Toronto, Toronto, Canada
2 Department of Medical Oncology, McGill University Health Centre, Montreal, Canada
3 Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada
Philippe L. Bedard, MD; e-mail: philippe.bedard@uhn.ca.
2024
27 6 2024
27 6 2024
8 e24000926 2 2024
28 3 2024
2 5 2024
© 2024 by American Society of Clinical Oncology
2024
American Society of Clinical Oncology
https://creativecommons.org/licenses/by-nc-nd/4.0/ Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/

PURPOSE

There is limited information about the clinical utility of targeted next-generation sequencing (NGS) panel testing to inform decision making for patients with advanced solid tumors. The Ontario-wide Cancer Targeted Nucleic Acid Evaluation (OCTANE) is a prospective study that enrolled more than 4,500 patients with solid tumor for NGS panel testing. We performed a retrospective survey of medical oncologists to evaluate the impact of NGS testing on treatment decisions.

METHODS

Patients and treating oncologists were identified at the Princess Margaret Cancer Center between 2016 and 2021. Tumor-only sequencing was performed using a gene panel of either 555 or 161 cancer genes. Oncologists were asked to review testing results and complete a survey indicating whether NGS testing affected treatment decisions. The primary outcome of this study was rate of treatment change on the basis of mutation results. Patient, test, and physician factors were evaluated for association with treatment changes using univariate analyses and a mixed-effects model.

RESULTS

Of the 582 surveys sent, 394 (67.7%) were completed. We found that 188 (47.7%) patients had testing results classified as actionable by the oncologist and 62 (15.7%) patients were matched to treatment, of whom 37 (60%) were enrolled in a clinical trial, 13 (21%) received an approved drug, four (6%) were prescribed off-label therapy, and eight (13%) avoided ineffective treatment. Patient, test, and physician characteristics were not significantly associated with treatment change. There was no difference in overall survival between patients who received matched treatment versus those who did not (P = .55, median survival not reached).

CONCLUSION

OCTANE testing led to a change in drug treatment in 15.7% of patients, supporting the clinical utility of NGS panel testing for patients with advanced solid tumors.

Tumor NGS panel testing can inform treatment decisions in patients with advanced solid tumors.

OPEN-ACCESSTRUE
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pmcBACKGROUND

Over the past decade, many targeted drug treatments have improved survival outcomes for patients whose tumors harbor oncogenic driver mutations, such as epidermal growth factor receptor (EGFR) and B-Raf (BRAF) inhibitors for patients with lung adenocarcinoma1 and melanoma,2 respectively. These targeted drugs were approved on the basis of clinical trials that used single-gene testing in common cancers with a high prevalence of sensitizing driver mutation(s) matched to targeted drug treatment.3,4 Technological advances with next-generation sequencing (NGS) now allow for routine testing of potentially drug-sensitizing genomic alterations in panels of genes that are frequently mutated across tumor types.

CONTEXT

Key Objective

How often does tumor next-generation sequencing (NGS) panel testing lead to a change in systemic drug treatment for advanced solid tumors?

Knowledge Generated

In a survey of medical oncologists at an academic center, 15.7% (62/394) of patients had treatment changed on the basis of NGS testing results, including enrollment in clinical trial, prescription of an approved drug, or avoidance of ineffective drug treatment. Possible reasons for not matching to treatment despite the presence of an actionable mutation included not only lack of treatment or clinical trial availability but also patient refusal and inability to receive further treatment because of clinical deterioration.

Relevance

This study provides insight into the clinical utility of NGS panel testing and the potential factors that influence treatment decision making for precision drug therapies.

Despite the increasing discovery of actionable mutations, the impact of pan-tumor NGS panel testing on clinical decision making for patients with advanced solid tumors remains uncertain. Reported rates of genotype-treatment matching, particularly with enrollment in clinical trials, vary widely between studies,5-15 from 3.6%13 to as high as 19%.5 Some studies have shown that NGS panel testing can lead to improved outcomes,5-10 but there is large variation between studies. Broad implementation of NGS panel testing across centers and cancer types is limited by cost-effectiveness, reimbursement, complexity of result interpretation, and mixed evidence regarding its clinical utility.3,16 As the landscape of actionable alterations continues to increase, there is an ongoing need to clarify the benefits and limitations of panel-based testing to guide its implementation.

The Ontario-wide Cancer Targeted Nucleic Acid Evaluation (OCTANE) is an ongoing prospective multi-institutional study that enrolled more than 4,500 patients with solid tumor for NGS panel testing with the objective to develop a provincial registry of testing results with molecularly and clinically annotated tumor tissues for future research.17 In this study, we performed a retrospective survey of medical oncologists enrolling OCTANE patients at the Princess Margaret Cancer Center (PM), a tertiary cancer center with a large advanced solid tumor patient population including specialized care for rare cancers, to evaluate the impact of NGS panel testing on treatment decisions across cancer types. Considering matched trial enrollment, prescription of approved treatments and avoidance of ineffective drug therapies, we hypothesized that NGS panel testing leads to a change in treatment in approximately 20% of patients tested.

METHODS

Patient and Physician Selection

The study was completed in two phases, with a first cohort of oncologists surveyed between 2017 and 2019 and a second cohort in 2021. Patients enrolled in OCTANE and their treating oncologists were identified at PM between 2016 and 2021. Oncologists who were no longer practicing at PM or had enrolled 12 or fewer OCTANE patients were excluded. A random sample was selected from all patients enrolled by the oncologists using the sample() function in R. The sample size for each oncologist was determined based on the number of patients they recruited in OCTANE and the initial survey response in the first cohort.

An overview of inclusion criteria and data collected in OCTANE are provided in Supplemental Methods. The OCTANE protocol was approved by the Ontario Cancer Research Ethics Board (ClinicalTrials.gov identifier: NCT02906943). Study participants consent to donate tumor tissue for NGS testing and future research, provide blood samples, and grant access to medical health records. Participants consent to deidentified clinical and genomic data-sharing for research.

Tumor NGS Testing

Formalin-fixed paraffin embedded (FFPE) tumor tissue was obtained for testing. Tumor-only sequencing was performed at the CAP/CLIA-certified University Health Network Advanced Molecular Diagnostics Laboratory using either a custom hybridization capture panel of 555 cancer-relevant genes (Hi5, SureSelect: Agilent, Santa Clara, CA) or a commercial 161-gene amplicon DNA/RNA panel (Oncomine Comprehensive Assay v3: ThermoFisher Scientific, Waltham, MA; Data Supplement). The OCTANE study transitioned from the Hi5 panel to Oncomine v3 in September 2018 because of the lower DNA input requirement and more streamlined informatics processing. The median turn-around time for processing of NGS results was 8.3 weeks.

A research report summarizing the sequencing results was sent to the ordering oncologist and annotated for clinical significance using the OncoKB therapeutic levels of evidence, a precision medicine knowledgebase recognized by the US Food and Drug Administration (FDA) in the United States.18 The OncoKB therapeutic levels are outlined in the Data Supplement. An OncoKB-identified actionable mutation was defined as a mutation at any OncoKB therapeutic level (including levels 1, 2, 3, 4, and R).

Survey Distribution

Oncologists were asked to complete self-administered questionnaires (Data Supplement) where they indicated if an actionable mutation was identified and if the NGS testing resulted in a treatment change. Oncologists had access to the OncoKB annotations in the NGS testing report, but actionable mutations were defined on the basis of clinical judgment.

A sample of 380 surveys was required to provide 95% confidence, assuming that the true rate of treatment change was 20% (± 4%). To facilitate survey completion, physicians were provided with a paper copy of the survey, the OCTANE testing report with OncoKB annotation, and their most recent clinical note. Oncologists were contacted through email, with a reminder sent if there was no initial response.

As treatment decisions may have changed between 2019 and 2021, follow-up surveys were sent for patients in the first cohort who had actionable mutations identified by the oncologist (regardless of OncoKB level), but no treatment change after initial survey completion.

Outcomes

The primary outcome of this study was rate of treatment change on the basis of mutation results. If treatment was changed, possible outcomes included (1) matching to a clinical trial, (2) prescription of an approved treatment, (3) off-label treatment, or (4) avoidance of ineffective therapy. If treatment was not changed, oncologists were asked to indicate why, with reasons including (1) no actionable mutation identified, (2) no trial available, (3) no off-trial therapy available, (4) patient declined treatment, (5) patient not suitable for treatment, (6) patient lost to follow-up, (7) patient deceased, or (8) other reason defined by the oncologist.

Secondary outcomes included treatment change on the basis of patient, test and physician factors, as well as overall survival.

Survival Data

Survival data were obtained from the institutional Cancer Registry. Survival information was supplemented by manual review of patient electronic medical records with documentation of the last patient clinic visit, vital status (alive/deceased), and date of death.

Survival time was taken from the date sequencing results were reported to date of death or the end of the follow-up period (November 10, 2021) when vital status was recorded. Patients who died before sequencing results were reported were excluded.

Statistical Analyses

Descriptive statistics were calculated to describe the patient and physician characteristics, the number of actionable mutations, mutation type, and rate of treatment change. To investigate factors associated with treatment change, univariate logistic regression models were fit to estimate the odds of treatment change on the basis of physician characteristics (experience, sex and patient enrollment in OCTANE) and patient factors (age, sex, panel type, mutation count, OncoKB level, time to sequencing). Mutation counts and time to sequencing were log-transformed before analysis. If a patient had mutations at multiple OncoKB therapeutic levels, the patient was categorized on the basis of the highest OncoKB level of evidence. To account for the correlated nature of the data (patients nested within physicians), models were fit using generalized estimating equations with an exchangeable working correlation structure and results confirmed using generalized mixed models with random physician intercepts using the geepack19 and lme420 packages, respectively. Kaplan-Meier curves of overall survival were created, and log rank tests were used to determine if survival varied by mutation levels or treatment changes. All analyses were performed in R version 4.2.3.21

RESULTS

Patient and Physician Cohort

Two cohorts of medical oncologists were surveyed, the first between 2017 and 2019 and the second in 2021. There were 10 and 14 medical oncologists surveyed in each cohort, with three of the oncologists participating in both cohorts. A total of 206 and 343 surveys were sent in the first and second cohorts, respectively, of which 172 (83.5%) and 222 (64.7%) were completed. Each medical oncologist completed surveys for a median of 19 patients (range, 9-48). Follow-up surveys were sent for patients with actionable mutations whose treatment did not change 1 year after initial survey completion in the first cohort. Of the 68 follow-up surveys sent, 56 (82%) were completed by 6 of 10 medical oncologists who received follow-up surveys. Each medical oncologist completed a median of nine follow-up surveys (range, 3-18; Fig 1).

FIG 1. Flow diagram of patients enrolled in OCTANE at Princess Margaret, surveys requested and completed, and impact on treatment decisions. OCTANE, Ontario-wide Cancer Targeted Nucleic Acid Evaluation.

Surveys were completed for a total of 394 patients across 25 tumor types, with responses from 21 medical oncologists. The most common primary tumor sites included breast (13%), head and neck (12%), bowel (9%), and pancreas (8%; Data Supplement, Table S1). Most physicians were female (66.7%), accounting for 60% of completed surveys (Data Supplement, Table S2). The median year of graduation from medical school for physicians was 2003. Individual medical oncologists enrolled a median of 56 patients in OCTANE (range, 16-245). The median patient age was 60 (range, 20-85) years, and patients were predominantly female (53%; Table 1). At the time of data lock, 63% of patients were alive, and the median survival time was not reached.

TABLE 1. Patient and Test Characteristics for the Entire Study (full sample) and Separated by Cohorts of Surveys Sent in 2019 and 2021, Respectively

Patient Characteristic	Full Sample, N = 394 (%)	2019, n = 172 (%)	2021, n = 222 (%)	
Patient age				
 Mean (SD)	57.6 (12.8)	57.0 (12.4)	58.0 (13.0)			
 Median (min, max)	59 (20, 84)	59 (27, 83)	60 (20, 84)			
Patient sex				
 Female	207 (53)	110 (64)	97 (44)			
 Male	187 (47)	62 (36)	125 (56)			
Vital status				
 Alive	248 (63)	100 (58)	148 (67)			
 Dead	146 (37)	72 (42)	74 (33)			
OncoKB level				
 None	189 (48)	77 (45)	112 (51)			
 Level 1	25 (6)	17 (10)	8 (4)			
 Level 2	66 (17)	33 (19)	33 (14)			
 Level 3	29 (7)	9 (5)	20 (9)			
 Level 4	80 (20)	32 (19)	48 (22)			
 Level R	5 (1)	4 (2)	1 (0)			
Gene panel				
 PM Hi5 Panel	240 (61)	164 (95)	76 (34)			
 PM Oncomine v3	154 (39)	8 (5)	146 (66)			
Mutation count				
 Median (min, max)	12 (0, 594)	17 (0, 594)	2 (0, 71)			
Abbreviation: PM, Princess Margaret Cancer Center.

Molecular Profiling

There were 61% of patients tested with the Hi5 panel and 39% with Oncomine v3 (Table 1). The median time from collection of archival tumor tissue to reporting was 403 days (range, 0-8,294 days). One or more mutations were detected in 352 (89%) patients, with a median mutation count of 12 per patient (range, 0-594). There were 203 patients who had a mutation considered potentially pathogenic by OncoKB at any therapeutic level. There were 5,749 mutations detected across all patients. Of these, 302 (5.3%) were considered actionable by OncoKB, with 8.6% classified as level 1, 27.5% level 2, 12.6% level 3, 49.7% level 4, and 1.6% level R.

Rate of Treatment Change on the Basis of NGS Results

There were 188 (47.7%) patients who had one or more NGS results classified as actionable by their medical oncologist, of whom 136 (72.3%) had ≥1 OncoKB-defined actionable mutation(s) (Fig 2A, Data Supplement, Tables S3 and S4). Of these 199 OncoKB alterations, 10.6% were classified as level 1, 30.6% level 2, 15.1% level 3, 41.2% level 4, 2.5% level R. Conversely, there were 69 (18%) patients who had an OncoKB-defined mutation which was not considered actionable by their medical oncologist. The highest therapeutic level for actionable mutations defined only by OncoKB was level 1 in 7% of these patients, level 2 in 2%, level 3 in 9%, level 4 in 62%, and level R in none (Data Supplement, Table S5).

FIG 2. Rate of treatment change on the basis of NGS testing results. (A) Patients are categorized as having treatment changed or not. Colors indicate if there was an actionable mutation identified by the oncologist, the OncoKB database, both, or neither. (B) Rationale for treatment decisions. (C) Matched treatments by drug category. Treatments are matched either as an approved drug or a clinical trial. (D) Actionable molecular phenotypes which resulted in treatment change. Unspecified refers to the two patients who had a mutation considered actionable by the oncologist, but the gene name was not indicated in the survey. NGS, next-generation sequencing.

There were 62 of 394 patients (15.7%) whose treatment decisions were influenced by the results of NGS testing, of whom 37 (60%) were enrolled in a clinical trial, 13 (21%) received an approved drug, four (6%) were prescribed off-label therapy, and eight (13%) avoided ineffective treatment (Fig 2B). Of the 54 patients who received matched treatment, the majority (71%) received targeted therapy, whereas 10% received a combination regimen (eg, targeted therapy with immunotherapy; Fig 2C). The presence or absence of alterations in RAS genes (including KRAS) was most frequently used by the medical oncologists to influence treatment decisions (3.2%). The next most frequent genes to influence treatment decisions were PIK3CA, ERBB2, and BRCA2, with mutation frequencies of 1%-2% for each gene (Fig 2D). The proportional impact on treatment decisions was the highest for colorectal (15/37, 40.5%), breast (14/52, 27.5%), biliary tract (6/22, 27.3%), and lung (4/17, 23.5%) cancers (Fig 3 and Data Supplement, Table S6). There were 127 of 188 (67.5%) patients with actionable mutations defined by the oncologist who did not receive treatment because of lack of available therapy, stability on current regimen, clinical deterioration, or patient decision. Of the 56 patients with actionable mutations whose treatment decisions were not influenced by NGS testing on the initial survey, five (9%) patients had a subsequent change in treatment decisions on the basis of NGS testing.

FIG 3. Treatment change by tumor site.

Treatment Change by Patient, Physician, and Test Factors

We assessed occurrence of treatment change by patient, physician, and test factors, controlling for correlation of patient outcomes within physicians. Treatment decisions were not associated with patient age, sex, physician clinical experience, physician sex, number of patients enrolled by the physician, panel type, OncoKB therapeutic level, or time from archival tumor tissue collection to sequencing (Table 2, Data Supplement, Tables S7 and S8).

TABLE 2. Patient, Test, and Physician Characteristics by Treatment Change

Factor	GEE, OR (95% CI)	GEE, P	n	Event	
Patient age	1.00 (0.98 to 1.03)	.78	188	62	
Patient sex (female/male)	0.89 (0.42 to 1.86)		90	27	
Gene panel (PM Hi5 Panel/PM Oncomine v3)	0.82 (0.43 to 1.58)		57	14	
Log(mutation count)	1.13 (0.90 to 1.40)	.29	188	62	
Log(time to sequencing)a	0.88 (0.70 to 1.11)	.28	186	61	
OncoKB level					
 None	Reference				
 Level 1	0.76 (0.17 to 3.43)	.72	20	7	
 Level 2	0.76 (0.31 to 1.89)	.55	51	16	
 Level 3	2.43 (0.72 to 8.27)	.15	23	12	
 Level 4	0.52 (0.23 to 1.15)	.11	37	6	
 Level R			5	5	
MD sex (female/male)	1.14 (0.34 to 3.82)		82	33	
MD experienceb (high/low)	0.51 (0.18 to 1.41)		111	30	
Patient enrollmentc (56 or less/more than 56)	1.22 (0.43 to 3.45)		102	41	
NOTE. Patient, test, and physician factors were evaluated using generalized estimating equations with an exchangeable working correlation structure, and results were confirmed using generalized mixed models with random physician intercepts. OR with 95% CI and P value reported.

Abbreviations: GEE, generalized estimating equations; OR, odds ratio; PM, Princess Margaret Cancer Center.

a Time to sequencing is calculated from time of sample collection to sequencing results.

b Physician experience was determined by date of graduation from medical school.

c Patient enrollment corresponds to the number of patients enrolled by each oncologist in the Ontario-wide Cancer Targeted Nucleic Acid Evaluation study.

Overall Survival

There was no difference in overall survival between patients who received treatment on the basis of NGS testing results and those who did not (log-rank P = .554, median survival not reached; Fig 4).

FIG 4. Overall survival by treatment change.

DISCUSSION

In this study, we assessed the clinical utility of NGS panel-based testing to guide treatment decisions in patients with advanced solid tumors. We found that 48% of patients had at least one mutation defined as actionable by the treating oncologist. This is comparable with the rate of actionable mutations reported in previous studies, which ranges from 33% to 71%.5,6,8,10-15 Many previous studies attempted to standardize the classification of clinical actionability of tumor genomic testing.18,22,23 OncoKB is an FDA-recognized knowledgebase implemented in the OCTANE reporting of NGS results to support physicians in their decision making. However, we found differences between oncologist and OncoKB-defined actionable mutations at any therapeutic level, as only 72% of alterations identified as actionable by the oncologist were considered actionable by OncoKB. Conversely, 18% of patients had a mutation identified as actionable by OncoKB, which was not considered actionable by the patient's oncologist. These differences highlight variations and subjectivity in the interpretation of NGS testing results, which is a barrier to NGS implementation in routine practice.24,25 It also suggests that knowledge bases such as OncoKB may be difficult to maintain as new clinical trials are developed. In this study, 7 of 11 (64%) patients who had treatment changed on the basis of a mutation considered actionable by the oncologist but not OncoKB were enrolled in a genotype-matched clinical trial (Data Supplement, Table S3).

Although 48% of patients had one or more actionable mutations identified by testing, only 15.7% had a treatment change on the basis of NGS testing results at the time of follow-up. This is consistent with previously reported rates of treatment matching, which vary widely between studies, from 3.6% to 19%.5-15 However, we note that the rate of treatment change increases as patients are followed over time, as 9% of patients with an actionable mutation only had treatment changed on follow-up 1 year after the first survey. This suggests that the long-term benefits of NGS testing may be underestimated by cross-sectional studies with short follow-up.

Given the observed variations in treatment matching for patients with actionable mutation(s), we explored the influence of patient, physician, and test factors on treatment decisions in our cohort. There is limited literature available assessing these factors. A previous study of 1,281 oncologists across the United States showed that oncologists were more likely to use NGS testing if they were younger, had a faculty appointment, genomics training, a higher patient load, or access to a molecular tumor board.26 In our study, patient, test, and physician characteristics were not associated with a higher likelihood of NGS-testing informed treatment decisions. It is noteworthy that in our study, testing with the lab-developed Hi5 NGS panel, which captures 555 genes, did not result in a greater likelihood of change in treatment decisions than the smaller Oncomine v3 panel, which captures 161 genes (Table 2). Although the type of panel was not randomized and driven by availability within the testing laboratory, this finding suggests that inclusion of a larger number of genes may not necessarily result in improved clinical utility.

An important measure of utility of NGS panel testing is the impact on clinical outcomes, including overall survival. In this study, there was no difference in overall survival between patients who had treatment changed on the basis of NGS results and those who did not. While a number of previous studies have shown that NGS panel testing can lead to improved treatment outcomes, the literature shows mixed results.5-10,27 Our results are consistent with previous studies that show that only a small proportion of patients tested subsequently receive matched treatment and derive clinical benefit.11

The are several limitations to our study. Access to matched treatment was not randomized among patients with actionable mutations. Our study was not powered to detect survival differences. The median survival was not yet reached in our cohort. It is noteworthy that OCTANE enrolled selected patients with advanced solid tumors with good performance status and available FFPE archival tumor tissue. The most common tumor types found in the general population28 with a higher proportion of actionable mutation(s) were relatively underrepresented in our cohort. There were fewer patients from tumor types where limited NGS tumor panel testing is a standard of care, such as melanoma, non–small cell lung cancer, and colorectal cancer. As the turn-around time for OCTANE testing results was 8 weeks, many patients were enrolled while they were still receiving standard-of-care treatment. In addition, tumor mutational burden was not assessed with the NGS panels used for testing. As a result of all these factors, our study may underestimate the impact of NGS testing on treatment decisions for patients with advanced solid tumors. Participation in our survey study was voluntary, reflected differences in return rates between oncologists surveyed, and assessment of the impact of NGS testing on treatment decisions was subject to recall bias. In addition, oncologists were not asked to justify why they changed treatment on the basis of a mutation that was not annotated as actionable by OncoKB.

However, our study design allowed us to evaluate differences in clinical practice in a real-world setting within a large-volume academic cancer center. Our study also includes a broader definition of impact on treatment decisions including off-label therapies and avoidance of ineffective treatment in addition to receipt of genotype-matched therapy in clinical trials.

Overall, OCTANE testing led to a change in drug treatment in 15.7% of patients in our study, supporting the clinical utility of NGS panel testing. Patient, test, and physician characteristics were not significantly associated with treatment change. Further studies evaluating the clinical utility of NGS testing are needed to better understand the impact on decision making in other health care settings.

PRIOR PRESENTATION

SUPPORT

AUTHOR CONTRIBUTIONS

Conception and design: Lucia Bogdan, Ramy R. Saleh, Philippe L. Bedard

Financial support: Philippe L. Bedard

Administrative support: Samanta Del Rossi, Philippe L. Bedard

Provision of study materials or patients: Philippe L. Bedard

Collection and assembly of data: Lucia Bogdan, Ramy R. Saleh, Samanta Del Rossi, Celeste Yu, Philippe L. Bedard

Data analysis and interpretation: Lucia Bogdan, Ramy R. Saleh, Lisa Avery, Philippe L. Bedard

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Presented at the ASCO Annual Meeting in Chicago, IL, June 5, 2022.

Supported by the Ontario Institute for Cancer Research through funding provided by the Government of Ontario (grant number P.OCT.051 and P.AO.075) and by the Princess Margaret Cancer Foundation.

Philippe L. Bedard

Research Funding: Bristol Myers Squibb (Inst), Sanofi (Inst), AstraZeneca (Inst), Genentech/Roche (Inst), GlaxoSmithKline (Inst), Novartis (Inst), Merck (Inst), Seagen (Inst), Lilly (Inst), Amgen (Inst), Bicara Therapeutics (Inst), Zymeworks (Inst), Medicenna (Inst), Bayer (Inst), Takeda (Inst), Gilead Sciences (Inst), LegoChem Biosciences (Inst), LegoChem Biosciences (Inst)

Uncompensated Relationships: Seagen, Zymeworks, Lilly, Roche/Genentech, Repare Therapeutics, Janssen Oncology

No other potential conflicts of interest were reported.
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