HER2-positive metastatic cervical cancer responsive to first and second-line treatment: A case report

Fortman, Dylan; Issa, Rochell; Stanbery, Laura; Albrethsen, Mary; Nemunaitis, John; Kasunic, Timothy

doi:10.1016/j.gore.2019.100520

Cited by 8 publications

(9 citation statements)

References 9 publications

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“…HER2 targeting drugs have demonstrated clinical efficacy against HER2-positive breast, gastroesophageal, and serous endometrial cancers, being the current therapeutic standards for these conditions and becoming investigational treatments in a continuously expanding set of solid tumors [ 13 – 17 ]. However, to our knowledge, no clinical trial assessing HER2 amplification/overexpression targeting agents in CC has been published to date, and the evidence of their successful use in this disease is limited to case reports [ 18 ]. The suitability of HER2 as an actionable target for clinical studies in CC would depend on HER2 positivity prevalence in this disease.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of HER2 overexpression and amplification in cervical cancer: A systematic review and meta-analysis

Itkin

García²,

Straminsky

et al. 2021

PLoS ONE

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The reported rates of HER2 positivity in cervical cancer (CC) range from 0% to 87%. The importance of HER2 as an actionable target in CC would depend on HER2 positivity prevalence. Our aim was to provide precise estimates of HER2 overexpression and amplification in CC, globally and by relevant subgroups. We conducted a PRISMA compliant meta-analytic systematic review. We searched Medline, EMBASE, Cochrane database, and grey literature for articles reporting the proportion of HER2 positivity in CC. Studies assessing HER2 status by immunohistochemistry or in situ hybridization in invasive disease were eligible. We performed descriptive analyses of all 65 included studies. Out of these, we selected 26 studies that used standardized American Society of Clinical Oncology / College of American Pathologists (ASCO/CAP) Guidelines compliant methodology. We conducted several meta-analyses of proportions to estimate the pooled prevalence of HER2 positivity and subgroup analyses using geographic region, histology, tumor stage, primary antibody brand, study size, and publication year as moderators. The estimated pooled prevalence of HER2 overexpression was 5.7% (CI 95%: 1.5% to 11.7%) I2 = 87% in ASCO/CAP compliant studies and 27.0%, (CI 95%: 19.9% to 34.8%) I2 = 96% in ASCO/CAP non-compliant ones, p < 0.001. The estimated pooled prevalence of HER2 amplification was 1.2% (CI 95%: 0.0% to 5.8%) I2 = 0% and 24.9% (CI 95%: 12.6% to 39.6%) I2 = 86%, respectively, p = 0.004. No other factor was significantly associated with HER2 positivity rates. Our results suggest that a small, but still meaningful proportion of CC is expected to be HER2-positive. High heterogeneity was the main limitation of the study. Variations in previously reported HER2 positivity rates are mainly related to methodological issues.

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Section: Introductionmentioning

confidence: 99%

Prevalence of HER2 overexpression and amplification in cervical cancer: A systematic review and meta-analysis

Itkin

García²,

Straminsky

et al. 2021

PLoS ONE

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“…6,7 Although HER2-targeting drugs (trastuzumab, pertuzumab, adotrastuzumab emtansine [TDM1], lapatinib) have improved survival in patients with HER2-positive lung, stomach, and cervical cancers, both inherent and developed resistance to HER2-targeting drugs still limit our effective management of this highly aggressive cancer subtype. [8][9][10] Therefore, effective HER2-targeted therapies for these patients are an unmet need, and efforts are being made to develop new anti-HER2 drugs.…”

Section: Introductionmentioning

confidence: 99%

Studies on the Safety and Efficacy of Pyrotinib in the Treatment of HER2- Positive Advanced Solid Tumors Excluding Breast Cancer

Yin¹,

Yang²,

Liu³

et al. 2020

CMAR

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Background: Human epidermal growth factor receptor 2 (HER2) is a member of the ErbB family and is a key proto-oncogene in solid tumors. This pilot study investigated the safety and efficacy of pyrotinib in HER2-positive non-breast advanced solid tumors. Patients and Methods: Twenty-five patients with HER2-positive advanced solid tumors excluding breast cancer were enrolled to receive pyrotinib-based therapy. The primary end point was progression-free survival (PFS). Results: The median PFS and overall survival (OS) were 3.5 months (95% CI: 2.2-5.0 months) and 9.6 months (95% CI: 4.4-9.9 months), respectively. Ten patients with lung cancer and 9 patients with gastric cancer had a median PFS of 2.5 months (95% CI: 0.97-6.53 months) and 2.9 months (95% CI: 1.50-7.17 months), respectively. The median OS was 9.9 months (95% CI: 4.4-9.9 months) in patients with lung cancer and 5.9 months (95% CI: 4.0-9.6 months) in patients with gastric cancer. No statistical significance of a median OS was observed, nonetheless, patients receiving > 3 lines had a numerically lower median OS than those receiving ≤ 3 lines of treatment (9.9 vs 5.1 months, P = 0.706). All 23 patients were available for efficacy evaluation. The objective response rate (ORR) was 52.17% and disease control rate (DCR) was 91.3%. The ORR for lung cancer was 44.4% and for gastric cancer was 50%. In addition, the DCR for lung cancer was 77.8% and for stomach cancer was 100%. Moreover, patients receiving ≤3 lines of treatment had a numerically higher DCR than those receiving >3 lines of treatment (94.1% vs 83.3%, P = 0.462). The most common treatment-related adverse events (TRAEs) were diarrhea (92%), but only 5 (20%) patients reported grade 3 diarrhea which could be well controlled. Conclusion: Pyrotinib-based therapy demonstrates promising efficacy for HER2-positive advanced solid tumors excluding breast cancer and toxicities could be well controlled. The study is a pilot study motivating larger studies to elucidate the safety and efficacy of pyrotinib in non-breast solid tumors.

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“…To determine whether these 23 candidate drugs had been previously associated with cervical cancer, we conducted an extensive literature search. We found that many of the drugs discovered had been used in or associated with cervical cancer ( 31 – 48 ) ( Table 1 ). Because studies in the literature generally do not include information on the HPV genotype of patients, we reviewed the drugs without considering HPV genotype to be on the safe side, and the drugs that had ever been associated with cervical cancer were not considered new in this study.…”

Section: Resultsmentioning

confidence: 99%

“…The combination of trastuzumab-pertuzumab, and the single-agent TDM-1, being effective in treatment of cervical cancer with HER2 amplification (48) interferon) is an unnatural synthetic interferon-alpha type 1 used to with chronic hepatitis C (57). Pimecrolimus was developed specifically for the treatment of inflammatory skin diseases (58).…”

Section: Discussionmentioning

confidence: 99%

Drug repositioning via host-pathogen protein-protein interactions for the treatment of cervical cancer

2023

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IntroductionIntegrating interaction data with biological knowledge can be a critical approach for drug development or drug repurposing. In this context, host-pathogen-protein-protein interaction (HP-PPI) networks are useful instrument to uncover the phenomena underlying therapeutic effects in infectious diseases, including cervical cancer, which is almost exclusively due to human papillomavirus (HPV) infections. Cervical cancer is one of the second leading causes of death, and HPV16 and HPV18 are the most common subtypes worldwide. Given the limitations of traditionally used virus-directed drug therapies for infectious diseases and, at the same time, recent cancer statistics for cervical cancer cases, the need for innovative treatments becomes clear.MethodsAccordingly, in this study, we emphasize the potential of host proteins as drug targets and identify promising host protein candidates for cervical cancer by considering potential differences between HPV subtypes (i.e., HPV16 and HPV18) within a novel bioinformatics framework that we have developed. Subsequently, subtype-specific HP-PPI networks were constructed to obtain host proteins. Using this framework, we next selected biologically significant host proteins. Using these prominent host proteins, we performed drug repurposing analysis. Finally, by following our framework we identify the most promising host-oriented drug candidates for cervical cancer.ResultsAs a result of this framework, we discovered both previously associated and novel drug candidates, including interferon alfacon-1, pimecrolimus, and hyaluronan specifically for HPV16 and HPV18 subtypes, respectively.DiscussionConsequently, with this study, we have provided valuable data for further experimental and clinical efforts and presented a novel bioinformatics framework that can be applied to any infectious disease.

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HER2-positive metastatic cervical cancer responsive to first and second-line treatment: A case report

Cited by 8 publications

References 9 publications

Prevalence of HER2 overexpression and amplification in cervical cancer: A systematic review and meta-analysis

Prevalence of HER2 overexpression and amplification in cervical cancer: A systematic review and meta-analysis

Studies on the Safety and Efficacy of Pyrotinib in the Treatment of HER2- Positive Advanced Solid Tumors Excluding Breast Cancer

Drug repositioning via host-pathogen protein-protein interactions for the treatment of cervical cancer

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