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. 2024 Sep;13(18):e70249.
doi: 10.1002/cam4.70249.

Real-world assessment of comprehensive genome profiling impact on clinical outcomes: A single-institution study in Japan

Kei Kunimasa  1   2 , Naotoshi Sugimoto  2   3 , Tomoyuki Yamasaki  2   4 , Yoji Kukita  2   5 , Fumie Fujisawa  2   6 , Tazuko Inoue  2 , Yuko Yamaguchi  2 , Mitsuko Kitasaka  2 , Daisuke Sakai  2   3 , Keiichiro Honma  7 , Toru Wakamatsu  8 , Sachiko Yamamoto  9 , Takuji Hayashi  10 , Seiji Mabuchi  11 , Jun Okuno  12 , Takahisa Kawamura  1 , Yugo Kai  13 , Makiko Urabe  13 , Kazuo Nishimura  2   10
Affiliations

Real-world assessment of comprehensive genome profiling impact on clinical outcomes: A single-institution study in Japan

Kei Kunimasa et al. Cancer Med. 2024 Sep.

Abstract

Introduction: Comprehensive genome profiling (CGP) has revolutionized healthcare by offering personalized medicine opportunities. However, its real-world utility and impact remain incompletely understood. This study examined the extent to which CGP leads to genomically matched therapy and its effectiveness.

Methods: We analyzed data from advanced solid tumor patients who underwent CGP panel between December 2019 and May 2023 at the Osaka International Cancer Institute. Patient demographics, specimen details, and expert panel assessments were collected. Turnaround time (TAT) and genomically matched therapy outcomes were analyzed. Gene alterations and their co-occurrence patterns were also assessed.

Results: Among 1437 patients, 1096 results were available for analysis. The median TAT was 63 [28-182] days. There were 667 (60.9%) cases wherein recommended clinical trials were presented and there were 12 (1.1%) cases that could be enrolled in the trial and 25 (2.3%) cases that could lead to therapies under insurance reimbursement. The median progression free survival of the trial treatment was 1.58 months (95% CI: 0.66-4.37) in clinical trials and 3.66 months (95% CI: 2.14-7.13) in treatment under insurance. Pathologic germline variants were confirmed in 15 patients (1.3%). Co-alteration of CDKN2A, CDKN2B, and MTAP was significantly observed in overall population.

Conclusion: The effectiveness of the genomically matched therapy based on the CGP panel was unsatisfactory. Expansion of clinical trials and utilization of remote clinical trials are required to ensure that the results of the CGP panel can be fully returned to patients.

Keywords: clinical trial; comprehensive genomic profiling; genomically matched therapy; real world data; solid tumor.

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Conflict of interest statement

Dr. Kunimasa reports honoraria for lecture from Chugai Pharma and Dr. Nishimura reports honoraria for lectures from Astellas, AstraZeneca, MSD, Janssen, Merck Biopharma and Bayer. The other authors have no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Patient flow chart. Flow chart of 1437 patients who consented to CGP panel evaluation.
FIGURE 2
FIGURE 2
Number of samples that underwent CGP panel by cancer type (A) and used CGP panel (B).
FIGURE 3
FIGURE 3
Box‐whisker plot of tumor mutation burden (TMB/Mb) per cancer type (A). TMB‐high (≥10/Mb) cases are shown in bar graphs for each cancer type (B). The figures in parentheses indicate the percentage of each cancer type among the total TMB‐high cases.
FIGURE 4
FIGURE 4
Co‐occurrence and mutual exclusivity of genetic alterations with significant interaction. The lower left region represents co‐occurrence (red), and the upper right region represents mutual exclusivity of genetic alterations (green).
FIGURE 5
FIGURE 5
Genomically matched therapy in clinical trial. List of patients enrolled, cancer type, genetic alterations treated, and drugs introduced (A). Kaplan–Meier curve showing the progression free survival for the patients (B).
FIGURE 6
FIGURE 6
Genomically matched therapy under insurance coverage. List of drugs introduced, and cancer types covered (A). Kaplan–Meier curve showing progression free survival for the patients (B). EGFR, Epidermal growth factor receptor; ERBB2, Erb‐b2 receptor tyrosine kinase 2; MET, MET proto‐oncogene; NSCLC, Non‐small cell lung carcinoma; PARP, Poly(ADP‐ribose) polymerases; SCLC, Small cell lung carcinoma; TMB, Tumor mutation burden.
FIGURE 7
FIGURE 7
List of cases with secondary findings that were identified as possible pathologic germline variants. The number of cases for each genetic variant is indicated by a bar graph. The cancer type is color‐coded in the graph.
See this image and copyright information in PMC

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