Yingyong Xu

In the last two decades, efforts in cancer treatment have been progressing rapidly in terms of scientific discoveries and development of new therapeutic solutions. Medical innovation contributes to significant survival gains for cancer patients. Yet, cancer remains one of the leading causes of death and one of the most pressing public health challenges worldwide. We propose an interpretative lens that refers to the idea of ‘anomaly’ as a driver of new technological paradigms to interpret new and emerging developments in medical innovation and in cancer treatment in particular. We use the lens of gateways to innovation and pathways of innovation to investigate how the organisation of (i) knowledge generation, (ii) technological applications and (iii) new clinical approaches emerge and are refined. We adopt a historical/longitudinal method following research and clinical outcomes in three ‘illustrative’ cases of cancer. Cancer is a heterogeneous, complex disease and is constantly evolving; thus, it remains a ‘persistent anomaly’. Research and clinical innovation activities have recently made great strides in understanding specific aspects of the disease and generated truly innovative therapeutic options in some areas, whilst in other areas, progress is lagging. At the same time, research and innovation activities have been employed to refine existing techniques, drugs and diagnostics providing improved treatment solutions across the related disease areas. Throughout its recent history, cancer research and innovation promoted several new paradigms tackling different aspects of the disease engendering new trajectories that have been implemented in conjunction with established and improved practices.

7548 Background: Gene expression profiling (GEP) is the gold standard in identification of activated B-cell-like (ABC) DLBCL, a subtype associated with inferior outcomes. The combination of lenalidomide + R-CHOP (R2-CHOP) provided efficacy based on cell-of-origin (COO) in phase II DLBCL studies. ROBUST is a global, randomized, double blind, phase III study comparing R2-CHOP vs placebo + R-CHOP in patients with previously untreated ABC-type CD20+ DLBCL (NCT02285062). Methods: ROBUST methods were previously described (Nowakowski, Fut Oncol 2016). Formalin-fixed paraffin-embedded excisional/surgical or core needle biopsy samples were analyzed by central pathology using the NanoString Lymphoma Subtyping Test (LST), based on the Lymph2Cx GEP assay (Scott, Blood 2014). Turnaround time was defined as number of days between central pathology sample receipt and results being provided to the study site. Results: From January 21, 2015 to August 3, 2017, 2093 patients were screened and 570 were enrolled in ROBUST. Three central pathology labs in China, USA and the UK received 2110 samples. Of 1798 successfully tested samples, COO was 788 (44%) ABC and 1010 (56%) non-ABC; 312 (15%) samples were non-processable for technical reasons (incorrect/insufficient slides or blocks, or low tissue RNA concentration and/or purity). According to geographic region of origin, the ABC-type DLBCL rate among successfully tested samples was 60% (241/404) from China/Japan/SK/Taiwan; 40% (441/1105) from Russia/Europe/Middle East; and 37% (106/289) from North America/Australia/New Zealand. Mean turnaround time was 2.4 days. Conclusions: Real-time COO assessment was feasible from multiple regions globally with a short turnaround time in the phase III ROBUST study, which minimizes the delay in receiving treatment. The percent of ABC-type DLBCL was similar to other reported studies of subtype analysis in the literature. Our findings impact the design and size estimation of future studies in newly diagnosed DLBCL utilizing COO as a biomarker, which provides a significant advance in precision medicine in DLBCL. Clinical trial information: NCT02285062.