The cohort was treated with the combination “and then we saw a very substantial number of patients that did respond,” he said.
Every patient with advanced disease treated at MSK undergoes tumor sequencing, which now numbers more than 12,000 annually. Patient and tumor details are entered into a database, giving principal investigators of basket studies “real-time access to patients who may benefit from these trials.”
Another significant advancement is the use of liquid biopsies, results of which can tell physicians whether a treatment is working within days, instead of up to 6 weeks on a CT scan, for example.
Liquid biopsies not only circumvent the need for patients to undergo repetitive tumor biopsies, but allow monitoring of tumor evolution such that clones can be detected as they emerge.
While pioneering, the basket study model is not a panacea for addressing the entire biologic context that is cancer.
Mutations may coexist, and other interactions may have an effect on clinical responses, such as the proteome, epigenome, and immune milieu.2
Dr. Baselga said he doubts the once-predicted “mutation” clinics will replace a breast cancer clinic, for example, primarily because most treatment is still driven by tumor origin. “Lineage still matters,” he said, “and this speaks to the complexity of cancer.”
He relayed the case of a patient with numerous metastases for which the tumor of origin could not be found, stymieing treatment efforts. When biopsied, the molecular profile pointed to a salivary gland tumor, which was confirmed on a subsequent scan.
The first use of the term “basket trial” can be traced to 2013 to Charles L. Sawyers, MD, chair of MSK’s Marie-Josée and Henry R. Kravis Center for Molecular Oncology. MSK has more than a dozen basket trials ongoing; most results will be reported over the next year.
In August 2015, the National Cancer Institute initiated enrollment for its phase 2 basket study, NCI-MATCH.3 Anticipated enrollment is 3,000 patients with solid tumors or lymphomas that have progressed following at least one line of standard treatment or for which no agreed-upon treatment approach exists.
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Tumors must have either activating mutations of epidermal growth factor receptor (EGFR) (del 19, L858R) by NCI-MATCH next-generation sequencing assay or any malignancy harboring any of the following mutations: EGFR G719A, G719C, G719D, G719S, EGFR L861Q, EGFR S768I, or EGFR T790M de novo or in combination with other mutations. Excluded are tumors with an exon 20 insertion alone without the previously mentioned mutations.
Interventions will include afatinib, crizotinib, dabrafenib, defactinib, the EGFR inhibitor AZD9291, sunitinib malate, trametinib, and trastuzumab emtansine. The primary outcome measure is objective response rate, defined as the percentage of patients whose tumors have a complete or partial response to treatment.
- Hyman DM, Puzanov I, Subbiah V, et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med. 2015;373(8):726-736.
- Thomas A, Lopez-Chavez A, Giaccone G. Reply to A. Stenzinger et al [correspondence]. J Clin Oncol. 2015;33(25):2824.
- ClinicalTrials.gov. EAY131: Molecular analysis for therapy choice (NCI-MATCH). NCT02465060. https://clinicaltrials.gov/ct2/show/NCT02465060. Verified August 15, 2015. Accessed September 15, 2015.