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Additional file 7. Supplemental Figs. 1–3. Supplemental Fig. 1. Histological findings of HER3 expression status. Surgical specimen of ovarian cancer (A); biopsy specimen of ovarian cancer (B); endometrial cancer (C); cervical cancer (D). Supplemental Fig. 2. Changes in HER3 expression between primary and recurrent status. Proportion of HER3-high at primary and recurrent status in ovarian cancer; high-grade serous carcinomas vs. others (A), platinum-sensitive recurrence vs. resistant recurrence (B), localized relapse vs. distant metastases (C), and one type of prior therapy vs. two or more (D). Proportion of HER3-high at primary and recurrent status in endometrial cancer; low-grade vs. high-grade (E), localized relapse vs. distant metastases (F), and non-chemotherapy vs. prior chemotherapy (G). Supplemental Fig. 3. Kaplan‒Meier survival analysis of overall survival, including changed HER3 status at recurrence. (A) ovarian cancer and (B) endometrial cancer in patients with HER3-decreased vs. patients with HER3-no chang vs. patients with HER3-increased at recurrence.

Additional file 4: Table S4. HER3 expression in ovarian cancer at initial diagnosis

Additional file 2: Table S2. Patient characteristics of endometrial cancer

Supplemental Material for Activation of neurons and satellite glial cells in the DRG produces morphine-induced hyperalgesia by Shunsuke Yamakita, Daisuke Fujita, Kazuki Sudo, Daiki Ishikawa, Kousuke Kushimoto, Yasuhiko Horii and Fumimasa Amaya in Molecular Pain.

Additional file 3: Table S3. Patient characteristics of cervical cancer

Additional file 6: Table S6. HER3 expression in cervical cancer at initial diagnosis

Additional file 2: Supplementary Table 1A. Multivariate analyses of relapse-free survival in 107 patients with common histological types. Supplementary Table 1B. Multivariate analyses of overall survival in 107 patients with common histological types.

Additional file 2. Univariate analyses of overall response rate.

Additional file 1. Patient characteristics excluding duplicate cases.

Additional file 1: Supplementary Figure 1. Representative microphotographs of mesothelin expression in each histological type. Squamous cell carcinoma (A and B), adenosquamous carcinoma (C and D), endocervical adenocarcinoma (usual-type) (E and F), gastric-type adenocarcinoma (G and H), and small cell neuroendocrine carcinoma (I and J). Haematoxylin & eosin stain: A, C, E, G, and I; immunohistochemical mesothelin staining: B, D, F, H, and J, original magnification ×200. Supplementary Figure 2. MSLN expression in paired specimens. Case 1 showed moderate MSLN expression in surgically resected tumour tissue (A, H-score = 120) and similar staining to the biopsy specimen of a metachronous recurrent tumour (B, H-score = 110). In contrast, Case 2 exhibited moderate to high MSLN expression in a surgically resected tumour (C, H-score = 150); however, MSLN expression was not detected in the biopsy specimen of a metastatic tumour (D, H-score = 0) (original magnification ×200). MSLN: mesothelin. Supplementary Figure 3. Kaplan–Meier RFS and OS analysis in all patients with respect to MSLN expression. Kaplan–Meier RFS and OS analysis with respect to MSLN expression. (A) RFS and (B) OS in patients with high MSLN expression versus those in patients with low MSLN expression. MSLN: mesothelin; OS: overall survival; RFS: relapse-free survival. Supplementary Figure 4. Kaplan–Meier RFS and OS analysis in patients with SCC or patients with AC and ASC with respect to MSLN expression. Kaplan–Meier RFS and OS analysis with respect to MSLN expression. (A) RFS and (B) OS in SCC patients with high MSLN expression versus those in patients with low MSLN expression. (C) RFS and (D) OS in AC and ASC patients with high MSLN expression versus those in patients with low MSLN expression. AC: adenocarcinoma; ASC: adenosquamous carcinoma; MSLN: mesothelin; OS: overall survival; RFS: relapse-free survival; SCC: squamous cell carcinoma.

Additional file 3. Univariate analyses of progression-free survival.

Additional file 3. Kaplan–Meier curves of second-line overall survival according to the number of cycles of first-line chemotherapy. OS, overall survival.

Additional file 2.

Additional file 5. Details of patients receiving nivolumab as second-line chemotherapy. ECOG, Eastern Cooperative Oncology Group; OS, overall survival; PFS, progression-free survival; PS, performance status.

Additional file 2. Univariate analysis of overall survival. CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; NA, not assessed; OS, overall survival; PS, performance status.

Additional file 4. Kaplan–Meier curves of overall survival according to the number of treatment lines. OS, overall survival.

Additional file 1.

Additional file 1. Treatment response in patients with measurable lesions. CI, confidence interval; DCR, disease control rate (complete response, partial response, and stable disease).

Background: Genetic alterations of FGFRs are known to play an important role in the proliferation, survival, and migration of cancer cells as well as tumor angiogenesis and drug resistance. E7090 is an orally available selective tyrosine kinase inhibitor for FGFR1-3. A global Phase 2 study of E7090 in subjects with unresectable advanced or metastatic cholangiocarcinoma harboring FGFR2 gene fusion is ongoing (NCT04238715). We recently reported FGFR alterations that are highly sensitive to E7090 using a high-throughput functional evaluation method called MANO method (Nakamura et al. npj Precision Oncology, 2021), narrowing down the most promising FGFR alteration targets. Here, we designed a single-arm, open-label, investigator-initiated multicenter Phase 2 basket study to evaluate the efficacy and safety of E7090 in subjects with advanced or recurrent solid tumors harboring FGFR gene alterations, focusing on alterations identified by MANO method, as a sub-study under the nationwide large registry for rare cancers in Japan (MASTER KEY Project). Methods: The key eligibility criteria are: 1) Histologically confirmed metastatic or locally advanced solid tumor; 2) Ineffective to or intolerant to first line treatment, or for which standard treatment is no longer available; and 3) Confirmed FGFR gene alterations via next-generation sequencing assays that are reimbursed by insurance. Subjects will receive E7090 140 mg orally once daily until disease progression or development of unacceptable toxicity. The primary endpoint is objective response rate (ORR) by independent central review (RECIST v1.1), and the secondary endpoints include ORR by investigator assessment, progression-free survival, overall survival, disease control rate, safety, duration of response, and time to response. For primary brain tumors, RANO criteria is also applied in assessment of response. The study enrolls approximately 45 subjects. (Clinical Trial Registry: jRCT2031210043, ClinicalTrials.gov: NCT04962867)