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Ribociclib plus endocrine therapy in premenopausal women with hormone receptor-positive, HER2-negative breast cancer
For pre- and postmenopausal patients with advanced, hormone receptor (HR)-positive, HER2-negative breast cancer, the addition of a cyclin-dependent kinase (CDK) 4/6 inhibitor (eg, ribociclib) to endocrine therapy has previously shown progression-free survival benefits, but its effect on overall survival has been unknown. In the randomized MONALEESA-7 trial, among almost 700 premenopausal patients with advanced HR-positive, HER2-negative breast cancer, the frontline addition of ribociclib to endocrine therapy improved the overall survival rate at 3.5 years (70 versus 46 percent) . We continue to recommend the addition of a CDK 4/6 inhibitor to endocrine therapy for most premenopausal women with advanced HR-positive, HER2-negative breast cancer.
Laparoscopic versus open distal gastrectomy for locally advanced gastric cancer
The efficacy of laparoscopic versus open distal gastrectomy for treatment of locally advanced gastric cancer is unclear. In a randomized trial comparing these procedures in over 1000 patients in China with clinically staged locally advanced gastric cancer, outcomes (overall survival, disease-free survival, cumulative recurrence) were similar for both approaches at three years follow-up . However, these results may have limited applicability to a Western population because about a third of patients were overstaged (ie, they had stage I tumors on pathology), none received perioperative therapy (which is typical in Western practice), and most Western patients have proximal (not distal) gastric cancers.
Enzalutamide or apalutamide plus androgen deprivation therapy for advanced castration-sensitive prostate cancer
Combining androgen deprivation therapy (ADT) with abiraterone or docetaxel, compared with ADT alone, prolongs overall survival in men with advanced castration-sensitive prostate cancer, and is now routinely recommended, especially for men with high-volume disease. Enzalutamide and apalutamide, second-generation antiandrogens, are approved by the US Food and Drug Administration (FDA) for men with castration-resistant prostate cancer. Two randomized trials (ENZAMET [ANZUP-1304]  and TITAN ) have now shown a survival benefit for the addition of enzalutamide or apalutamide to ADT versus ADT alone for initial treatment of advanced castration-sensitive prostate cancer. However, there are no trials of ADT plus enzalutamide or apalutamide compared with ADT plus either abiraterone or docetaxel in this setting. Pending results of such trials, we continue to recommend treatment with ADT and either abiraterone or docetaxel for these patients.
Pembrolizumab in metastatic, PD-L1 positive cervical cancer
For women with metastatic cervical cancer who have progressed following frontline combination chemotherapy, single-agent chemotherapy has been standard, although immunotherapy is being evaluated for those with tumor programmed death-ligand 1 (PD-L1) expression. In a phase II study, among over 80 women with advanced, pretreated cervical cancer and PD-L1 expression of 1 percent or more, the objective response rate with pembrolizumab was 15 percent, and the median duration of response had not been reached at a median follow-up of 10 months . Based on these results, the US Food and Drug Administration approved pembrolizumab for those with metastatic, PD-L1 positive cervical cancer that has progressed on chemotherapy, and we now consider it an acceptable option in this setting.
Long-term survival benefit from BRAF and MEK inhibition in BRAF V600 mutation-positive metastatic melanoma (June 2019)
The combination of a BRAF and an MEK inhibitor (eg, dabrafenib and trametinib, respectively) is standard of care for patients with BRAF V600 mutation-positive metastatic melanoma. Two major phase III trials (COMBI-d and COMBI-v) have demonstrated survival benefit for dabrafenib and trametinib relative to single-agent BRAF inhibition. In a pooled analysis of over 900 patients assigned to dabrafenib and trametinib in these trials, estimated five-year overall and progression-free survival rates were 34 percent and 19 percent, respectively, with five years of follow-up . Favorable prognostic factors included normal LDH and <3 organ sites with metastatic disease. This long-term follow-up provides further support for dabrafenib and trametinib for patients with BRAF V600 mutation-positive metastatic melanoma.
Pemetrexed and cisplatin as adjuvant therapy for nonsquamous NSCLC
Although vinorelbine is commonly administered with cisplatin as adjuvant chemotherapy for resected non-small cell lung cancer (NSCLC), a previous phase II trial suggested that pairing cisplatin with pemetrexed may be an effective and better-tolerated option for those with nonsquamous NSCLC. Now, in preliminary results of a phase III trial including almost 800 patients with resected stage II to IIIA nonsquamous NSCLC, median recurrence-free survival and three-year overall survival rates were similar among those assigned to pemetrexed versus vinorelbine (with cisplatin in either case) . Patients in the pemetrexed group had less neutropenia and higher completion rates. As adjuvant treatment for those with resected nonsquamous NSCLC, we suggest pemetrexed rather than vinorelbine to partner with cisplatin, due to similar efficacy and better tolerability.
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2. Yu J, Huang C, Sun Y, et al. Effect of Laparoscopic vs Open Distal Gastrectomy on 3-Year Disease-Free Survival in Patients With Locally Advanced Gastric Cancer: The CLASS-01 Randomized Clinical Trial. JAMA 2019; 321:1983.
3. Davis ID, Martin AJ, Stockler MR, et al. Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. N Engl J Med 2019.4. Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med 2019.
5. Chung HC, Ros W, Delord JP, et al. Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol 2019; 37:1470.
6. Robert C, Grob JJ, Stroyakovskiy D, et al. Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma. N Engl J Med 2019.
7. Kenmotsu H, Yamamoto N, Yamanaka T, et al. Randomized phase III study of pemetrexed/cisplatin (Pem/Cis) versus vinorelbine /cisplatin (Vnr/Cis) for completely resected stage II-IIIA non-squamous non-small-cell lung cancer (Ns-NSCLC): The JIPANG study. J Clin Oncol 2019; 37S: ASCO #8501.
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