Non-small cell lung cancer clinical trials requiring biopsies with biomarker-specific results for enrollment provide unique challenges.

BACKGROUND: Clinical trials in lung cancer increasingly require patients to provide fresh tumor tissue as a prerequisite to enrollment. The effects of this requirement on enrollment rates, enrollment durations, and patient selection have not been fully elucidated. METHODS: The authors retrospectively reviewed data generated by patients who consented to 1 or more interventional lung cancer clinical trials at the University of California-Los Angeles Jonsson Comprehensive Cancer Center between January 2013 and December 2014. Trials were considered to require a biopsy when enrollment was conditional on the procurement of tissue without intervening therapy between procurement and enrollment. RESULTS: In total, 311 patients underwent 368 screening incidents for 1 or more of 19 trials. Trials that required a new biopsy had a longer median screening duration (34 vs 14 days) than trials that did not require a biopsy (P < .001). Trials that required a biopsy had a greater screen failure rate (49.1% vs 26.5%; P < .001), which was largely driven by patients who did not undergo the required biopsy or lacked the required biomarker. Worsening performance status led to the majority of screen failures (56.5%) among biomarker-eligible patients. CONCLUSIONS: Although the scientific benefits of obtaining a new biopsy and requiring specific results for trial enrollment are clear, these requirements lead to a lengthening of the screening period, which, in some patients, is associated with clinical decline before enrollment. Implications for the interpretation of data from studies of this design should be explored. Cancer 2017;123:4800-7. © 2017 American Cancer Society.

Clinical Implications of the T790M Mutation in Disease Characteristics and Treatment Response in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small-Cell Lung Cancer (NSCLC).

BACKGROUND: The secondary T790M mutation accounts for more than 50% of acquired tyrosine kinase inhibitor (TKI) resistance in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). Recent reports suggest this resistance mutation may be more common among patients with longer progression-free survival (PFS) on first-line TKI therapy, but much is still unknown. MATERIALS AND METHODS: Our group collected medical records from patients who underwent a biopsy for T790M mutation testing while screening for clinical trials involving the drug rociletinib (CO-1686), a T790M mutation-specific TKI. Medical records were retrospectively analyzed for demographic data, PFS, and best response to previous therapies. RESULTS: Our patient cohort included 69 T790M+ patients and 28 T790M- patients. Patients who later developed a T790M mutation had a longer PFS on first-line TKI therapy (12.0 vs. 9.0 months, P = .021), but overall response rate (ORR) was the same (75.0% vs. 81.0%, P = .76). There was no difference in PFS on TKI rechallenge (4.0 vs. 3.0 months, P = .94), although there was a trend toward higher ORR in T790M+ patients (22.2% vs. 0%, P = .12). T790M+ patients had a longer PFS on initial chemotherapy treatment (5.0 vs. 4.0 months, P = .025) and a trend toward higher ORR (40.0% vs. 21.4%, P = .31). CONCLUSION: Our study confirms that tumors expressing T790M have a more indolent progression of disease compared with their T790M- counterparts when treated with both first-line TKI and cytotoxic chemotherapy.

Clinical Trials in Non-Small Cell Lung Cancer with Biomarker-Driven Treatment Allocation: Ready or Not, Here We Come.

Lung cancer is the leading cause of cancer mortality. Great advances in non-small cell lung cancer therapy have been seen in the last decade, beginning with the success in treating lung cancer harboring EGFR mutations and ALK-gene rearrangements. The potential of these biomarker-driven therapies has propelled research in biomarker targeted approaches to the forefront of lung cancer research. The successful development of immunotherapeutic agents targeting PD-L1 and PD-1 with an associated non-genomic biomarker has opened a new front in the effort for targeted approaches. Although early-phase lung cancer studies have hinted at the potential to use biomarkers to select patients for allocation to treatment in the conduct of clinical trials, data from late-phase studies have tempered expectations. The data leave unclear the wisdom of routinely restricting enrollment on lung cancer clinical trials to biomarker restricted populations, particularly non-genomic biomarkers.

Representing and extracting lung cancer study metadata: study objective and study design.

This paper describes the information retrieval step in Casama (Contextualized Semantic Maps), a project that summarizes and contextualizes current research papers on driver mutations in non-small cell lung cancer. Casama׳s representation of lung cancer studies aims to capture elements that will assist an end-user in retrieving studies and, importantly, judging their strength. This paper focuses on two types of study metadata: study objective and study design. 430 abstracts on EGFR and ALK mutations in lung cancer were annotated manually. Casama׳s support vector machine (SVM) automatically classified the abstracts by study objective with as much as 129% higher F-scores compared to PubMed׳s built-in filters. A second SVM classified the abstracts by epidemiological study design, suggesting strength of evidence at a more granular level than in previous work. The classification results and the top features determined by the classifiers suggest that this scheme would be generalizable to other mutations in lung cancer, as well as studies on driver mutations in other cancer domains.