Challenges for the implementation of high-throughput testing and liquid biopsies in personalized medicine cancer trials.

During recent decades, major advances in the comprehension of biology and in biotechnologies have paved the way for what is commonly named personalized medicine. For cancer therapy, personalized medicine represents a paradigm shift in which patient treatment is based on biology in addition to histology and tumor location. Here, we report the major personalized medicine trials in oncology that are either based on molecular alterations from tumor tissue or from circulating blood markers. We next review important challenges facing the implementation of personalized medicine in daily clinical practice, including tumor heterogeneity, reliability of high-throughput technologies, the key role of bioinformatics and the assessment of biomarkers and synthetic models, in order to use big data in actual cancer biology.

First-line chemoimmunotherapy in metastatic breast carcinoma: combination of paclitaxel and IMP321 (LAG-3Ig) enhances immune responses and antitumor activity.

BACKGROUND: IMP321 is a recombinant soluble LAG-3Ig fusion protein that binds to MHC class II with high avidity and mediates APC and then antigen-experienced memory CD8+ T cell activation. We report clinical and biological results of a phase I/II in patients with metastatic breast carcinoma (MBC) receiving first-line paclitaxel weekly, 3 weeks out of 4. METHODS: MBC patients were administered one dose of IMP321 s.c. every two weeks for a total of 24 weeks (12 injections). The repeated single doses were administered the day after chemotherapy at D2 and D16 of the 28-day cycles of paclitaxel (80 mg/m2 at D1, D8 and D15, for 6 cycles). Blood samples were taken 13 days after the sixth and the twelfth IMP321 injections to determine sustained APC, NK and memory CD8 T cell responses. RESULTS: Thirty MBC patients received IMP321 in three cohorts (doses: 0.25, 1.25 and 6.25 mg). IMP321 induced both a sustained increase in the number and activation of APC (monocytes and dendritic cells) and an increase in the percentage of NK and long-lived cytotoxic effector-memory CD8 T cells. Clinical benefit was observed for 90% of patients with only 3 progressors at 6 months. Also, the objective tumor response rate of 50% compared favorably to the 25% rate reported in the historical control group. CONCLUSIONS: The absence of toxicity and the demonstration of activity strongly support the future development of this agent for clinical use in combined first-line regimens. TRIAL REGISTRATION: ClinicalTrials.gov NCT00349934.