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PURPOSE We previously reported on the pilot study assessing the feasibility of using the Japanese translation of the Comprehensive Score for Financial Toxicity (COST) tool to measure financial toxicity (FT) among Japanese patients with cancer. In this study, we report the results of the prospective survey assessing FT in Japanese patients with cancer using the same tool. PATIENTS AND METHODS Eligible patients were receiving chemotherapy for a solid tumor for at least 2 months. In addition to the COST survey, socioeconomic characteristics were collected by using a questionnaire and medical records. RESULTS Of the 191 patients approached, 156 (82%) responded to the questionnaire. Primary tumor sites were colorectal (n = 77; 49%), gastric (n = 39; 25%), esophageal (n = 16; 10%), thyroid (n = 9; 6%), head and neck (n = 4; 3%), and other (n = 11; 7%). Median COST score was 21 (range, 0 to 41; mean ± standard deviation, 12.1 ± 8.45), with lower COST scores indicating more severe FT. On multivariable analyses using linear regression, older age (β, 0.15 per year; 95% CI, 0.02 to 0.28; P = .02) and higher household savings (β, 8.24 per ¥15 million; 95% CI, 4.06 to 12.42; P < .001) were positively associated with COST score; nonregular employment (β, −5.37; 95% CI, −10.16 to −0.57; P = .03), retirement because of cancer (β, −5.42; 95% CI, −8.62 to −1.37; P = .009), and use of strategies to cope with the cost of cancer care (β, −5.09; 95% CI, −7.87 to −2.30; P < .001) were negatively associated with COST score. CONCLUSION Using the Japanese version of the COST tool, we identified various factors associated with FT in Japanese patients with cancer. These findings will have important implications for cancer policy planning in Japan.

The applicability of circulating tumor DNA (ctDNA) genotyping to inform enrollment of patients with cancer in clinical trials has not been established. We conducted a phase 2 trial to evaluate the efficacy of pertuzumab plus trastuzumab for metastatic colorectal cancer (mCRC), with human epidermal growth factor receptor 2 (HER2) amplification prospectively confirmed by tumor tissue or ctDNA analysis (UMIN000027887). HER2 amplification was confirmed in tissue and/or ctDNA in 30 patients with mCRC. The study met the primary endpoint with a confirmed objective response rate of 30% in 27 tissue-positive patients and 28% in 25 ctDNA-positive patients, as compared to an objective response rate of 0% in a matched real-world reference population treated with standard-of-care salvage therapy. Post hoc exploratory analyses revealed that baseline ctDNA genotyping of HER2 copy number and concurrent oncogenic alterations adjusted for tumor fraction stratified patients according to efficacy with similar accuracy to tissue genotyping. Decreased ctDNA fraction 3 weeks after treatment initiation associated with therapeutic response. Pertuzumab plus trastuzumab showed similar efficacy in patients with mCRC with HER2 amplification in tissue or ctDNA, showing that ctDNA genotyping can identify patients who benefit from dual-HER2 blockade as well as monitor treatment response. These findings warrant further use of ctDNA genotyping in clinical trials for HER2-amplified mCRC, which might especially benefit patients in first-line treatment.

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BackgroundFinancial toxicity (FT) has a negative impact on the quality of life and survival of patients with cancer. The comprehensive score for FT (COST) questionnaire is a tool to measure FT which has already been validated in patients with cancer in the United States. However, the feasibility and validity of assessing FT using the COST questionnaire have not been established in non-US healthcare settings, including that in Japan.MethodsThis is a prospective pilot survey to ascertain the feasibility of using the COST questionnaire to evaluate FT in Japanese patients with advanced solid cancer who had been receiving chemotherapy for at least 2 months. The COST questionnaire was translated into Japanese using Functional Assessment of Chronic Illness Therapy methodology.ResultsOf the 12 patients approached, 11 (92%) responded to the questionnaire. The median COST score was 22 (range, 6–29; mean ± SD, 20.18 ± 8.17). Five (45%) and two (18%) patients suffered grade 1 (COST score 14–25) and grade 2 (COST score 1–13) FT, respectively. The COST measure demonstrated good internal consistency with a Cronbach α of 0.87.ConclusionsThe COST measure demonstrated good feasibility in measuring FT in the Japanese healthcare setting. Despite the existing universal health insurance system and ceiling amount for high-cost medical expenses, some Japanese patients experienced meaningful FT during chemotherapy. A prospective study is already underway to confirm the preliminary results (UMIN: 000025043).

4000 Background: T-DXd is an antibody-drug conjugate composed of an anti-HER2 antibody, cleavable tetrapeptide-based linker, and topoisomerase I inhibitor payload. Early studies have shown promising activity in advanced HER2-expressing tumors. DESTINY-CRC01 (DS8201-A-J203; NCT03384940) is a phase 2, open-label, multicenter study of T-DXd in pts with HER2-expressing mCRC. Methods: Pts with centrally confirmed HER2-expressing, RAS–wild type mCRC that progressed on ≥ 2 prior regimens received T-DXd 6.4 mg/kg every 3 weeks (q3w) in 3 cohorts (A: HER2 IHC 3+ or IHC 2+/ISH+; B: IHC 2+/ISH−; C: IHC 1+). The primary endpoint was confirmed objective response rate (ORR) by independent central review in cohort A; secondary endpoints included, disease control rate (DCR; CR + PR + SD), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and ORR in cohorts B and C. Results: At data cutoff (Aug 9, 2019), 78 pts (A, 53; B, 7; C, 18) had received T-DXd. Median age was 58.5 y (range, 27-79 y), 52.6% of pts were male, and 89.7% had left colon or rectum cancer; median number of prior regimens was 4 (range, 2-11); all pts had prior irinotecan. Median treatment duration was 3.5 mo (95% CI, 2.1-4.3 mo; cohort A, 4.8 mo [95% CI, 3.9-5.8 mo]); 38.5% of pts remained on T-DXd treatment. The confirmed ORR was 45.3% (24/53 pts; 95% CI, 31.6%-59.6%) in cohort A, including 1 CR and 23 PRs; median DOR was not reached (95% CI, 4.2 mo-NE). The ORR in pts with prior anti-HER2 treatment was 43.8% (7/16 pts; 95% CI, 19.8%-70.1%). The DCR was 83.0% (44/53 pts; 95% CI, 70.2%-91.9%); median PFS was 6.9 mo (95% CI, 4.1 mo-NE); median OS was not reached. No responses were observed in cohorts B or C. Grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred in 61.5% of pts (48/78); the most common (≥10%) were decreased neutrophil count (21.8%) and anemia (14.1%). Seven pts (9.0%) had TEAEs leading to drug discontinuation. Five pts (6.4%) had interstitial lung disease (ILD) adjudicated by an independent committee as related to T-DXd (2 grade 2; 1 grade 3; 2 grade 5 [the only drug-related deaths]). Conclusions: Overall, T-DXd 6.4 mg/kg q3w demonstrated remarkable activity in pts with HER2-expressing mCRC refractory to standard therapies, with a safety profile consistent with previous results. ILD is an important risk and requires careful recognition and intervention. Clinical trial information: NCT03384940 .

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