There are now many studies that support the thesis that patients who receive a treatment matched to a tumor molecular profile have a longer progression free survival (PFS). Von Hoff et al JCO 2010;28 4877-4883, Tsimberridou et al., Clin Cancer Res 2014;20 4827-4836, Schwaederle et al (Abstract 11097) presented at ASCO summarized the analysis of 570 Phase II Studies of single agents published from 2010-2012 encompassing 32,149 patients across malignancy types. They concluded that a “personalized strategy was independently associated with higher response rates, longer PFS and overall survival, as well as fewer toxic deaths”. The “non-personalized targeted arms led to poorer outcomes than cytotoxics”. Intermountain Health published 2 compelling studies in abstract form. The first study was an internal retrospective health economic analysis of 72 patients, 36 of who received treatment match to a NGS molecular profile and 36 matched control patients (age, gender, histological diagnosis and previous treatment lines) who received chemotherapy. The PFS was 22.9 weeks for the “precision medicine” treatment group and 12 weeks for the historical control group. Costs per week were $3204 per week in the targeted group and $3501 in the control cohort. They concluded that additional survival is not associated with increased healthcare costs although it is clear that the overall cost is increased since these patients lived longer. Additionally, the costs of treatment-related morbidities is significantly lower for patients receiving genomic cancer medicine compared to standard chemotherapy approaches. (Nadauld et al.,J Clin Oncol 33, 2015 (suppl; abstr e17641)). In a second study the Intermountain Health group studied the impact of NGS results on physician decision making for 243 patients with a variety of tumor types. 188 patients (77%) had actionable mutation. The NGS results changed treatment decisions with 117 patients being treated with a targeted drug while an additional 38 patients (20%) have targeted options available but are awaiting disease progression from their current treatment. (Nadauld et al., J Clin Oncol 33, 2015 (suppl; abstr e17647).
SHIVA is a randomized phase II trial comparing therapy based on tumor molecular profiling versus conventional therapy in patients with refractory cancer (the feasibility part of this trial was presented at ASCO 2015 Le Tourneau et al Abstract 11113). This is the only trial that shows no PFS benefit for therapy selected via molecular profiling.
The other ongoing and planned randomized control trials (Summary in Herbst et al Clin Cancer Res 2015;21 1541-1524) include Umbrella trials such as BATTLE, Lung-Map, Focus 4 etc. and Basket Trials such as NCI MATCH (launched at the meeting), MD Anderson’s M-PACT and IMPACT 2 and of course ASCO’s own TAPUR trial also announced at the meeting. The Novartis Signature trial program is also a very innovative tissue agnostic, genetic alteration-specific signal finding set of studies with trial sites being opened wherever an eligible patient is identified. Between March 2013 – January 2015, 16 academic and 151 unique community/network sites have dosed 368 pts; buparlisib (142), dovitinib (73), binimetinib (90), encorafenib (9), ribociclib (30), BGJ398 (12), ceritinib (3) and sonidegib (9) with completed cohorts for buparlisib (CRC, ovarian, sarcomas, HNSCC, cervix), dovitinib (CRC, GIST), and binimetinib (lung). Preliminary activity was observed in various tumors; buparlisib (vaginal, HNSCC), dovitinib (ovarian), and binimetinib (AML, ovarian, thyroid). This data is expected to lead to subsequent confirmatory trials.
The one caveat here for all these studies is that molecular profiling means different things to different people!