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Alpelisib and fulvestrant in PIK3CA mutant breast cancer (March 2021)

For patients with advanced, ER-positive, HER2-negative breast cancer that harbors a PIK3CA mutation and has progressed on previous aromatase inhibitor (AI) therapy, the addition of the phosphoinositide 3-kinase (PI3K) inhibitor alpelisib to fulvestrant has shown progression free survival benefits. However, it was unknown whether alpelisib would be effective after progression on an AI plus a cyclin dependent kinase (CDK) 4/6 inhibitor, a preferred frontline regimen. In a single-arm phase II study in 127 patients with tumor PIK3CA mutations and prior AI/CDK 4/6 inhibitor treatment, approximately 50 percent of patients receiving alpelisib plus fulvestrant had not progressed after six months on treatment [1]. For patients with advanced, ER-positive, HER2-negative breast cancer that harbors a PIK3CA mutation and has progressed on an AI, with or without a CDK 4/6 inhibitor, we suggest alpelisib plus fulvestrant.

USPSTF lung cancer screening recommendations (March 2021)

Many expert groups recommend lung cancer screening for individuals at high risk. New guidelines from the US Preventive Services Task Force (USPSTF) expand the recommended screening population to adults age 50 to 80 years old who are at high risk due to smoking history (at least a 20 pack-year smoking history and are either current smokers or have quit within the past 15 years) [2]. Previously, the target population was adults 55 to 80 years of age with at least a 30 pack-year smoking history. Screening consists of annual low-dose computed tomography and is not recommended for persons with limited life expectancy. We agree with the USPSTF guidelines, but also note that prevention by promoting smoking cessation remains the most important strategy to reduce lung cancer mortality.

Postoperative nivolumab after initial chemoradiotherapy for esophageal and esophagogastric junction cancer (April 2021)

Patients with localized esophageal or esophagogastric junction (EGJ) cancer who are treated with neoadjuvant chemoradiotherapy and have residual disease at the time of resection remain at high risk for recurrence and death from cancer, yet optimal postoperative management is unknown. In the CheckMate 577 trial of nearly 800 such patients, adjuvant nivolumab for up to one year doubled median disease-free survival compared with placebo (22.4 versus 11 months) without adversely affecting health-related quality of life [3]. Benefits were seen across all patient subgroups (histology, location, initial and posttreatment disease stage) and did not depend on programmed cell death ligand-1 status. Overall survival data are not yet mature. Based on these results and the morbidity of disease recurrence, we now suggest one year of adjuvant nivolumab for patients with resected esophageal or EGJ cancer who have residual disease in the surgical specimen after initial chemoradiotherapy.

Tebentafusp for metastatic uveal melanoma (April 2021)

Metastatic uveal melanoma is a rare, aggressive malignancy with few effective treatment options. There is interest in developing novel T-cell receptor therapeutics for this disease, such as tebentafusp, which specifically targets glycoprotein 100, a uveal melanoma antigen. In preliminary results from a phase III trial of almost 400 patients with positive human leukocyte antigen-A*0201 and systemic treatment-naive advanced uveal melanoma, tebentafusp improved overall survival (OS) compared with investigator's choice of immunotherapy or chemotherapy (one-year OS 73 versus 59 percent) [4]. These data are promising, and we await regulatory approval of tebentafusp prior to incorporating it into routine clinical practice.

Endoscopic nasopharyngectomy for patient with locoregionally recurrent nasopharyngeal carcinoma (April 2021)

For select patients with locoregionally recurrent nasopharyngeal carcinoma (NPC), options include salvage surgery or reirradiation, but the optimal approach is not established. In an open-label, randomized phase III trial of 200 patients with recurrent NPC, endoscopic nasopharyngectomy (ENPG) improved three-year overall survival (OS) compared to reirradiation with intensity-modulated radiotherapy (86 versus 68 percent) and had less long-term toxicity [5]. Based on these data, we suggest salvage surgery with ENPG rather than reirradiation for patients with recurrent clinical stage T1 to T2 NPC who are eligible for resection. However, radiation therapy is a reasonable alternative for those who are ineligible for or decline surgery.

1. Rugo HS, Lerebours F, Ciruelos E, et al. Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study. Lancet Oncol. 2021;22(4):489.

2. US Preventive Services Task Force, Krist AH, Davidson KW, Mangione CM, et al. Screening for Lung Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2021;325(10):962.

3. Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med. 2021;384(13):1191.

4. Piperno-Neumann S, Hassel JC, Rutkowski P, et al. CT002 - Phase 3 randomized trial comparing tebentafusp with investigator's choice in first line metastatic uveal melanoma. In: Proceedings of the 112th Annual Meeting of the American Association for Cancer Research; 2021 April 10-15. Philadelphia (PA): AACR; 2021. Abstract CT002. Cancer Res. 2021; https://www.abstractsonline.com/pp8/#!/9325/presentation/5133%20.

5. Liu YP, Wen YH, Tang J, et al. Endoscopic surgery compared with intensity-modulated radiotherapy in resectable locally recurrent nasopharyngeal carcinoma: a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021;22(3):381. Epub 2021 Feb 15.

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