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Pembrolizumab plus neoadjuvant chemotherapy in triple negative breast cancer

Immunotherapy is used for metastatic triple negative breast cancer (TNBC), but its role in early breast cancer is not established. Now, in KEYNOTE-522, the addition of the checkpoint inhibitor pembrolizumab to standard neoadjuvant chemotherapy among patients with early TNBC improved pathologic complete response rates (65 versus 51 percent) and event-free survival rates (93 versus 88 percent) at a follow-up of about 16 months [1]. Grade >=3 toxicities were similar with and without pembrolizumab. While the preliminary results from KEYNOTE-522 are encouraging, it is not yet routine to add checkpoint inhibitors to neoadjuvant chemotherapy in TNBC.


BRAF inhibition versus combined BRAF/MEK inhibition plus cetuximab for progressive RAS wild-type BRAF mutated metastatic colorectal cancer

For patients with RAS wild-type metastatic colorectal cancer (mCRC) and a BRAF V600E mutation (BRAF mut), resistance to epidermal growth factor receptor (EGFR)-targeted agents may be overcome with BRAF inhibitors, with or without a MEK inhibitor. The phase III BEACON trial established triplet therapy using cetuximab plus the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib as an effective strategy to overcome EGFR inhibitor resistance in these patients [2]. However, in a later analysis with longer follow-up, there was no longer a difference in median overall survival between the two targeted regimens, and quality-of-life improvements were similar, although there was still a slightly higher response rate with the triplet combination [3]. For most patients we now prefer doublet therapy with encorafenib plus cetuximab over triplet therapy.


HMG-CoA reductase gene variant and epithelial ovarian cancer

While there are a number of known genetic risk factors for ovarian cancer, protective genetic factors have not been well established. Now, in a case control study of over 63,000 patients, those with genetic variants leading to reduced activity in the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase were found to have decreased rates of epithelial ovarian cancer (odds ratio [OR] 0.60) [4]. Although HMG-CoA reductase is the limiting step in cholesterol biosynthesis and the target of statin medications, this study did not evaluate statins themselves, and further research is needed to determine whether statins are associated with reduced ovarian cancer risks.


Patient-reported outcomes with pembrolizumab and chemotherapy

For patients with advanced, nonsquamous non-small cell lung cancer (NSCLC), the KEYNOTE-189 trial previously demonstrated improved survival outcomes with the addition of the checkpoint inhibitor pembrolizumab to chemotherapy. Now, in subsequent reporting, patient-reported quality of life scores are also improved among those receiving pembrolizumab and chemotherapy versus chemotherapy alone [5]. These results support our approach of treating patients with advanced, programmed cell death-ligand 1 (PD-L1) unselected or low advanced NSCLCs with pembrolizumab and chemotherapy. Based on other data, we continue to treat most patients with PD-L1 high advanced NSCLC with pembrolizumab alone.


Updated cancer statistics in the US

Cancer is a global health problem and a leading cause of death in the United States. The 2020 estimates of new cancer cases and deaths in the US have been reported, based on data collected through 2017, and suggest that the overall cancer death rate in the US has dropped by 29 percent in the past three decades [6]. This steady improvement is attributed largely to reductions in smoking and subsequent declines in lung cancer mortality, resulting in the largest ever single-year drop in overall cancer mortality of 2.2 percent from 2016 to 2017. However, treatment breakthroughs have also contributed, for example with immunotherapies and targeted therapies in melanoma.


1. Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med 2020; 382:810.


2. Kopetz S, Grothey A, Yaeger R, et al. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer. N Engl J Med 2019; 381:1632.


3. Kopetz S, Grothey A, Van Cutsem E, et al. Encorafenib plus cetuximab with or without binimetinib for BRAF V600E-mutant metastatic colorectal cancer: Quality-of-life results from a randomized, three-arm, phase III study versus the choice of either irinotecan or FOLFIRI plus cetuximab (BEACON CRC) (abstract). J Clin Oncol 38, 2020(suppl4; abstr 8). (Accessed on February 18, 2020).


4. Yarmolinsky J, Bull CJ, Vincent EE, et al. Association Between Genetically Proxied Inhibition of HMG-CoA Reductase and Epithelial Ovarian Cancer. JAMA 2020; 323:646.


5. Garassino MC, Gadgeel S, Esteban E, et al. Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously untreated, metastatic, non-squamous non-small-cell lung cancer (KEYNOTE-189): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 2020; 21:387.


6. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69:7.


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