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With a plethora of new oncology research at your disposal, it can be difficult to keep track of the latest innovations and findings. Oncology Times is offering our readers summaries of the newest studies to keep you abreast of advancements across the spectrum of oncology care.


Mitochondrial "power" drives tamoxifen resistance: NQO1 and GCLC are new therapeutic targets in breast cancer


While the reasons are unknown, approximately 50 percent of breast cancer patients treated with the estrogen receptor-blocking drug tamoxifen eventually become resistant. Researchers hypothesized that a mechanism of this resistance is related to energy-generating mitochondria in cancer cells. In a new study, these investigators identified the protein NQO1 as the trigger that determines whether cells would survive tamoxifen or not (Oncotarget 2017; doi:10.18632/oncotarget.15852). Investigators directly compared sensitive cells with tamoxifen-resistant cancer cells, and demonstrated that higher mitochondrial power is what distinguishes a drug-sensitive cell from a resistant cell. A combination of protein profiling, genetics, and metabolism were utilized to identify which genes were necessary to confer tamoxifen-resistance. Researchers observed that, by adding just a single gene, NQO1, the cells would survive. Tamoxifen-resistant cells were then successfully sensitized using a chemical inhibitor of NQO1 (dicoumarol). "We speculate that pharmacological inhibition of NQO1 and GCLC may be new therapeutic strategies for overcoming tamoxifen-resistance in breast cancer patients," researchers concluded. "These findings could have important translational significance for the prevention of tumor recurrence in ER(+) breast cancers, which is due to an endocrine resistance phenotype. Importantly, we also show here that NQO1 has significant prognostic value as a biomarker for the prediction of tumor recurrence."


Diagnostic comparison of CT scans and colonoscopy for immune-related colitis in ipilimumab-treated advanced melanoma patients


In a recent study, researchers retrospectively assessed 303 patients with metastatic melanoma who had been treated with ipilimumab at Dana-Farber Cancer Institute, Boston, between 2008 and 2015 to determine whether CT scans provide a safer, faster, and more cost-effective alternative to reliably diagnoses colitis (Cancer Immunol Res 2017; doi:10.1158/2326-6066.CIR-16-0302). Investigators reported that 33 percent of the patients (99) who received ipilimumab experienced diarrhea and other gastrointestinal (GI) symptoms concerning for colitis; 46 of these patients were diagnosed with immune-related colitis based on either direct visualization and biopsy of the colonic mucosa or the need for corticosteroid for resolution of the GI symptoms. Thirty of the 46 patients with colitis had undergone both colonoscopy/biopsy and CT. After correlating the CT scans with the biopsy results, researchers found that CT scans had a 96 percent positive predictive value. "We conclude that CT is a fast, reliable, and noninvasive mode of diagnosing colitis, whereas colonoscopy and biopsy may not be needed to establish that diagnosis," authors wrote.


High-throughput genomics and clinical outcome in hard-to-treat advanced cancers: results of the MOSCATO 01 trial


New data found that cancer patients treated with targeted therapies had a significantly higher progression-free survival rate (PFS) than patients treated with a previous line of therapy (Cancer Discov 2017; doi:10.1158/2159-8290.CD-16-1396). Between 2011 and 2016, investigators enrolled 1,035 adult patients with advanced, unresectable, or metastatic cancer that had progressed after at least one line of prior therapy. A tumor biopsy was obtained from 948 patients and DNA sequencing was performed on 843. An actionable target was identified in 411 patients, and of these patients, 199 received a targeted therapy that matched the genomic alteration identified, according to researchers. Among these patients, the most frequent alterations were observed in the genes PIK3CA, ERBB2, PTEN, FGFR1, EGFR, and NOTCH. The ratio between PFS on matched therapy/PFS on prior therapy was >1.3 in 33 percent of the patients (63/193), investigators reported. Median overall survival was 11.9 months (95% CI, 9.5-14.3 months). "This study suggests that high-throughput genomics could improve outcomes in a subset of patients with hard-to-treat cancers," researchers concluded. "Although these results are encouraging, only 7 percent of the successfully screened patients benefited from this approach." Randomized trials are necessary to determine the benefit of this approach.


Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma


Results of a randomized controlled phase III trial found that adding hematopoietic stem cell transplantation (HSCT) to lenalidomide, bortezomib, and dexamethasone (RVD) improved progression-free survival (PFS) among multiple myeloma patients (NEJM 2017; doi:10.1056/NEJMoa1611750). Seven-hundred patients were randomly assigned to receive RVD, alone or with HSCT. The primary endpoint was PFS; secondary endpoints included response rate, time-to-disease progression, overall survival, and adverse events. Researchers reported that the median PFS was longer in patients treated with RVD and transplantation compared to those who received RVD alone (50 months vs. 36 months). "Among adults with multiple myeloma, RVD therapy plus transplantation was associated with significantly longer progression-free survival than RVD therapy alone, but overall survival did not differ significantly between the two approaches," investigators concluded.


Effect of total laparoscopic hysterectomy vs. total abdominal hysterectomy on disease-free survival among women with stage I endometrial cancer


In a recent study, researchers sought to answer the question, "Is total laparoscopic hysterectomy equivalent to total abdominal hysterectomy for early-stage endometrial cancer surgery?" Data found there were similar rates of disease-free survival and no difference in overall survival among women who received a laparoscopic or abdominal total hysterectomy for stage I endometrial cancer (JAMA 2017; doi:10.1001/jama.2017.2068). Patients were randomly assigned to one of two groups, either total abdominal hysterectomy (TAH; n=353) or total laparoscopic hysterectomy (TLH; n=407). At 4.5 years, disease-free survival was was 81.6 percent with total laparoscopic hysterectomy compared to 81.3 percent with total abdominal hysterectomy. There was no statistically significant between-group difference in recurrence of endometrial cancer (7.9% in the TAH group vs. 8.1% in the TLH group) or in overall survival (6.8% in the TAH group vs. 7.4% in the TLH group). The authors concluded, "These findings support the use of laparoscopic hysterectomy for women with stage I endometrial cancer."