Vascular endothelial growth factor-A is an Immunohistochemical biomarker for the efficacy of bevacizumab-containing chemotherapy for duodenal and jejunal adenocarcinoma

Amano, Takahiro; Iijima, Hideki; Shinzaki, Shinichiro; Tashiro, Taku; Iwatani, Shuko; Tani, Mizuki; Otake, Yuriko; Yoshihara, Takeo; Sugimoto, Aya; Egawa, Satoshi; Yamaguchi, Shinjiro; Kinoshita, Kazuo; Araki, Mikiya; Hirao, Motohiro; Sakakibara, Yuko; Hiyama, Satoshi; Ogawa, Hiroyuki; Nagaike, Koji; Murata, Jun; Komori, Masato; Okuda, Yuji; Kizu, Takashi; Tsujii, Yoshiki; Hayashi, Yoshito; Inoue, Takahiro; Takahashi, Hidekazu; Mizushima, Tsunekazu; Morii, Eiichi; Takehara, Tetsuo

doi:10.1186/s12885-021-08724-5

Cited by 6 publications

(14 citation statements)

References 30 publications

(34 reference statements)

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“…After full-text revision, 57 studies were included, with a total of 35 176 patients. Among the 57 studies, 6 studies 27 , 28 , 29 , 30 , 31 , 32 were prospective cohort studies or phase 2 trials, and 51 studies 1 , 3 , 4 , 17 , 19 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 were retrospective in nature ( Table ; eTables 1 and 2 in…”

Section: Resultsmentioning

confidence: 99%

“…Studies in the palliative setting commonly studied all SIA localizations. Twenty-six studies 3 , 17 , 27 , 28 , 29 , 30 , 32 , 33 , 35 , 44 , 46 , 48 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 68 , 70 , 72 , 74 , 75 , 76 , 77 (65.0%) specified the chemotherapy regimens. Targeted agents were investigated in 7 studies, 31 , 60 , 61 , 63 , 64 , 71 , 76 of which most assessed bevacizumab.…”

Section: Resultsmentioning

confidence: 99%

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Evaluation of Systemic Treatments of Small Intestinal Adenocarcinomas

et al. 2023

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ImportanceAlthough small intestinal adenocarcinomas (SIAs) are rare, they have a poor prognosis, and the optimal treatment strategies are largely unknown. Because of the lack of high-quality evidence, guidelines for colorectal cancer are often followed in the treatment of SIAs.ObjectiveTo review the current evidence regarding survival benefit of systemic therapies, including chemotherapy, targeted agents, and immunotherapy, for patients with SIAs.Data SourcesFollowing the Preferred Reporting Items for Systematic Reviews and Meta-analyses, MEDLINE and Embase were searched for articles published from January 1, 2005, until June 1, 2022.Study SelectionRetrospective cohort studies and prospective phase 2 or 3 trials describing survival after systemic therapies for patients with SIAs were eligible for inclusion. Assessment of study eligibility was blinded and performed by 3 reviewers.Data Extraction and SynthesisThe reviewers independently extracted data. Random effects, inverse variance, pairwise meta-analyses were performed.Main Outcomes and MeasuresPrimary outcomes were overall survival (OS) and progression-free survival (PFS) of patients with SIAs after systemic therapies. Measures of interest included hazard ratios for survival and median survival times.ResultsOverall, 57 retrospective cohort and phase 2 studies of 35 176 patients were included. Adjuvant chemotherapy, generally fluoropyrimidine-based, was associated with increased OS in stage I to III SIAs (hazard ratio [HR], 0.60; 95% CI, 0.53-0.68), especially in stage III tumors (HR, 0.55; 95% CI, 0.48-0.64), irrespective of tumor localization. Palliative chemotherapy was also associated with an OS benefit (HR, 0.48; 95% CI, 0.40-0.58). Fluoropyrimidine-oxaliplatin combinations were superior to other regimens (OS: HR, 0.54; 95% CI, 0.30-0.99; PFS: HR, 0.46; 95% CI, 0.30-0.71). Furthermore, bevacizumab added to chemotherapy compared with chemotherapy alone was associated with significantly prolonged PFS (HR, 0.62; 95% CI, 0.43-0.89). Immunotherapy showed a 50% overall response rate in previously treated defective mismatch repair tumors.Conclusions and RelevanceIn this systematic review and meta-analysis, adjuvant and palliative chemotherapy were both associated with improved survival of patients with SIAs, especially fluoropyrimidine-based regimens and fluoropyrimidine-oxaliplatin combinations. Adding bevacizumab to chemotherapy appears to prolong PFS and deserves further investigation. Immunotherapy seems beneficial and should be considered for patients with defective mismatch repair tumors. International collaborations should be undertaken to confirm and improve efficacy of systemic therapies for patients with SIAs.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Evaluation of Systemic Treatments of Small Intestinal Adenocarcinomas

et al. 2023

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“…The role of anti-angiogenic therapies, such as bevacizumab or ramucirumab, which were well established in metastatic CRC, underwent limited evaluation in advanced SBA, despite the known importance of the VEGF pathway in SBA [ 29 ]. Indeed, immunohistochemical expression of VEGF-A was recently reported as a potentially useful biomarker for the prediction of the efficacy of bevacizumab-based treatment in patients with advanced SBA [ 30 ].…”

Section: Targeted Therapiesmentioning

confidence: 99%

Therapeutic Strategies for Patients with Advanced Small Bowel Adenocarcinoma: Current Knowledge and Perspectives

Moati

Overman

Zaanan

2022

Cancers

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Small bowel adenocarcinoma (SBA) is diagnosed at an advanced (unresectable or metastatic) tumor stage in approximately one-third of cases. This is partly due to the non-specific symptomatology and limitations in endoscopic and radiologic detection methods. In this context, the prognosis remains poor and systemic chemotherapy appears to benefit patients when compared to best supportive care alone, despite the absence of randomized controlled trials. The results of a recent large prospective cohort (ARCAD-NADEGE) reported that the absence of chemotherapy was a predictive factor for a lower overall survival (OS) even though poor differentiation and SBA associated with Crohn’s disease correlate with poor prognosis. In retrospective series, the median OS ranges from approximately 9 to 18 months with current treatment approaches. A combination of a fluoropyrimidine and oxaliplatin (FOLFOX or CAPOX) appears to be the most utilized and effective first-line chemotherapy regimen. Other front-line alternatives are the combination of 5-FU and cisplatin or fluoropyrimidine and irinotecan (FOLFIRI). In second-line, FOLFIRI is an effective option after progression on platinum-based therapy. Taxane-based therapy appears to be an alternative option, but further evaluation in larger series is needed. To a limited extent, the role of surgical resection for metastatic disease appears to be a valid option, though this approach has not been evaluated in prospective clinical studies. Due to the rareness of the disease, inclusion in clinical trials should be prioritized, and there is hope that targeted therapies and immunotherapy may enter the therapeutic arsenal for these patients.

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“…Despite the lack of statistical comparison, the mPFS of XELOX plus bevacizumab is comparable to that of XELOX alone, as reported by the same institution (6). However, another retrospective multicenter study reported an mPFS of 15 months in 10 metastatic duodenal and jejunal adenocarcinoma patients treated with bevacizumab plus platinum (19). Notably, among patients treated with bevacizumab-based regimens, the mPFS of six patients with high vascular endothelial growth factor-A (VEGF-A) expression was significantly higher than four patients with low VEGF-A expression, implying that VEGF-A expression might act as a predictor for bevacizumab efficacy.…”

Section: Anti-vascular Therapymentioning

confidence: 55%

Case report: A case of duodenal adenocarcinoma achieving significantly long survival treating with immune checkpoint inhibitors and chemotherapy without positive biomarkers

Chen

Zhou

et al. 2022

Front. Immunol.

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Small bowel adenocarcinoma (SBA), particularly duodenal adenocarcinoma (DA), is a rare gastrointestinal cancer with a dismal prognosis. Data on SBA treatments are limited, and the therapeutic strategy remains uncertain. Currently, chemotherapy is the most used treatment; however, it has a poor median progression-free survival (mPFS) of no more than five months in the second-line setting. We report a case with DA that responded well to the immune checkpoint inhibitor (ICI) tislelizumab plus irinotecan in the second-line treatment. To our knowledge, this is the first report of administering ICIs plus chemotherapy to SBA. Despite the absence of microsatellite instability-high (MSI-H) and high tumor mutational burden (TMB), the patient with TP53/KRAS mutation achieved a significantly long PFS of 17 months, and the benefit is still ongoing. The mechanism of this remarkable efficacy might be associated with an increase in tumor immunogenicity after chemotherapy. The current study presents a promising effect of ICIs plus chemotherapy on SBA, affirming the need to investigate the clinical value of this combination in SBA and the underlying mechanism behind it.

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Vascular endothelial growth factor-A is an Immunohistochemical biomarker for the efficacy of bevacizumab-containing chemotherapy for duodenal and jejunal adenocarcinoma

Cited by 6 publications

References 30 publications

Evaluation of Systemic Treatments of Small Intestinal Adenocarcinomas

Evaluation of Systemic Treatments of Small Intestinal Adenocarcinomas

Therapeutic Strategies for Patients with Advanced Small Bowel Adenocarcinoma: Current Knowledge and Perspectives

Case report: A case of duodenal adenocarcinoma achieving significantly long survival treating with immune checkpoint inhibitors and chemotherapy without positive biomarkers

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