Future Clinical Trials

Astsaturov, Igor

doi:10.1016/j.soc.2017.05.014

Cited by 4 publications

(3 citation statements)

References 41 publications

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“…However, we did not observe responses in two patients who received MTAs. This is consistent with the initial results of clinical trials looking at the use of MTAs in prospective fashion 33,34. For instance, in SAPHIR01 trial, for women with metastatic BC, 13% of patients were able to receive MTAs based on the genomic data and of those patients, only 9% had objective tumor response 35.…”

supporting

confidence: 82%

Paired tumor sequencing and germline testing in breast cancer management: An experience of a single academic center

et al. 2020

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Background: Genetic testing for cancer predisposition is recommended to women with breast cancer who meet the criteria for such testing. After the FDA approvals of the poly ADP ribose polymerase (PARP) inhibitors, olaparib and talazoparib, for treatment of metastatic breast cancer, carrying germline mutations in BRCA1 and BRCA2 genes, the genetic testing result has become critical in their care. With the recent FDA approval of alpelisib for the treatment of PIK3CA-mutated hormone-receptor positive metastatic breast cancer, tumor molecular profiling to identify somatic mutations and potential molecularly targeted agents is increasingly utilized in the treatment of advanced breast cancer. Aim: Combining germline and somatic sequencing (paired testing) offers an advantage over a single technique approach. Our study evaluates the role of paired testing on the management of breast cancer patients. Methods and Results: Forty-three breast cancer patients treated at Rush University Medical Center underwent paired germline and somatic variant testing in 2015 to 2017. A retrospective chart review was conducted with the analysis of demographic, clinical, and genomic data. Three actionable germline variants were found in the CHEK2 (2) and ATM (1) genes. 95% of tumors had somatic mutations. Seventy-seven percent of tumors had genomic alterations targetable with agents approved for breast cancer and 88% had molecular targets for agents approved for other cancers. Clinical examples of such use are described and potential future directions of tumor and paired testing are discussed. Conclusions: Germline variants were present in a relatively small patient group not routinely tested for inherited alterations. Potentially targetable somatic alterations were identified in the majority of breast cancers. Paired testing is a feasible and

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confidence: 82%

Paired tumor sequencing and germline testing in breast cancer management: An experience of a single academic center

et al. 2020

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“…To address these questions, a novel clinical design called a “basket trial” was developed. This is a new clinical trial paradigm that determines eligibility based on the presence of a specific genomic alteration, irrespective of histology (1, 47, 48). Unlike traditional clinical trials which focus on patients with a single cancer histology, the core organizing principle of basket trials focused on a specific genomic alteration found in the tumor, regardless of where the cancer originated (Figure 2).…”

Section: Basket Trialsmentioning

confidence: 99%

Basket Trials for Intractable Cancer

et al. 2019

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Currently, genomic characterization has become standard of care for tumor types such as non-small cell lung cancer, breast cancer, melanoma, and colorectal cancer. A deep understanding of genomic alterations in different tumor types would help identify potentially actionable genomic changes which occur across a wide variety of tumor types. A basket trial is a new type of clinical trial for which eligibility is based on the presence of a specific genomic alteration, irrespective of histology. Basket trials are phase II screening trials for the off-label use of a targeted drug in patients with the same genomic alterations for which it was approved. Intractable cancer refers to a type or condition of cancer which is unresponsive or resistant to treatment; intractable cancers may be classified into five subtypes as follows: hard-to-treat condition of common advanced cancer after multiple-line therapy, rare cancer in which no standard of care has been recommended, advanced cancer in which standard of care does not work well, cancer accompanied with organ dysfunction, and cancers in older or younger cancer patients. Previous studies have demonstrated that in basket trials, genomic-guided therapy yields clinical benefits in intractable cancer, thereby providing novel insights into the optimal clinical management of such cancers. In this review, we describe a novel way to classify intractable cancer, and summarize the current knowledge on such cancers. We additionally provide information on the role of basket trials in intractable cancer.

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“…To this end, a novel clinical trial design referred to as a "basket trial", was developed. This study design focuses on specific gene alterations found in tumors, regardless of the location of cancer origins (6)(7)(8). Based on prior basket trials investigating the presence of specific gene alterations, a few of therapeutic strategies have been approved for pan-cancer patients independent of cancer types (i.e., larotrectinib for neurotrophic tyrosine kinase, receptor, type (NTRK) 1-3 fusion, pembrolizumab for mismatch repair high deficiency/ microsatellite instability, and pembrolizumab for high tumor mutation burden [TMB]; >10 mut/Mb]) (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Targeted therapy for intractable cancer on the basis of molecular profiles: An open-label, phase II basket trial (Long March Pathway)

et al. 2023

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PurposeWe evaluated he effects of molecular guided-targeted therapy for intractable cancer. Also, the epidemiology of druggable gene alterations in Chinese population was investigated.Materials and methodsThe Long March Pathway (ClinicalTrials.gov identifier: NCT03239015) is a non-randomized, open-label, phase II trial consisting of several basket studies examining the molecular profiles of intractable cancers in the Chinese population. The trial aimed to 1) evaluate the efficacy of targeted therapy for intractable cancer and 2) identify the molecular epidemiology of the tier II gene alterations among Chinese pan-cancer patients.ResultsIn the first stage, molecular profiles of 520 intractable pan-cancer patients were identified, and 115 patients were identified to have tier II gene alterations. Then, 27 of these 115 patients received targeted therapy based on molecular profiles. The overall response rate (ORR) was 29.6% (8/27), and the disease control rate (DCR) was 44.4% (12/27). The median duration of response (DOR) was 4.80 months (95% CI, 3.33−27.2), and median progression-free survival (PFS) was 4.67 months (95% CI, 2.33−9.50). In the second stage, molecular epidemiology of 17,841 Chinese pan-cancer patients demonstrated that the frequency of tier II gene alterations across cancer types is 17.7%. Bladder cancer had the most tier-II alterations (26.1%), followed by breast cancer (22.4%), and non-small cell lung cancer (NSCLC; 20.2%).ConclusionThe Long March Pathway trial demonstrated a significant clinical benefit for intractable cancer from molecular-guided targeted therapy in the Chinese population. The frequency of tier II gene alterations across cancer types supports the feasibility of molecular-guided targeted therapy under basket trials.

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Future Clinical Trials

Cited by 4 publications

References 41 publications

Paired tumor sequencing and germline testing in breast cancer management: An experience of a single academic center

Paired tumor sequencing and germline testing in breast cancer management: An experience of a single academic center

Basket Trials for Intractable Cancer

Targeted therapy for intractable cancer on the basis of molecular profiles: An open-label, phase II basket trial (Long March Pathway)

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