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Atezolizumab plus neoadjuvant chemotherapy for triple negative breast cancer

Trials are evaluating the incorporation of immunotherapy into the neoadjuvant management of triple negative breast cancer (TNBC). In the IMpassion031 trial, among over 300 patients with treatment-naive stage II-III TNBC, the addition of the PD-L1-targeted monoclonal antibody atezolizumab to neoadjuvant chemotherapy improved pathologic complete response rates (58 versus 41 percent) [1]. While promising, previous data are mixed, and the effect on long-term outcomes remains unknown. Pending further data, we do not incorporate immunotherapy into the neoadjuvant management of patients with TNBC.


Pembrolizumab for advanced cutaneous squamous cell carcinoma

For patients with advanced cutaneous squamous cell carcinoma (SCC) not curable with local therapies, checkpoint inhibitor immunotherapy is an effective and well-tolerated treatment option. In an open-label phase II trial (KEYNOTE-629) of approximately 100 patients with locally advanced recurrent or metastatic cutaneous SCC, the programmed cell death-1 (PD-1) inhibitor pembrolizumab demonstrated an objective response rate of 34 percent and a one-year overall survival of 60 percent, and was well-tolerated [2]. These data led to the US Food and Drug Administration approval of pembrolizumab in patients with recurrent or metastatic cutaneous SCC not curable with surgery or radiation therapy [3]. In these patients, we offer either pembrolizumab or cemiplimab, as both of these PD-1 inhibitors have regulatory approval in this setting.


Adjuvant targeted therapy for stage III BRAF-mutant melanoma

For patients with BRAF V600-positive stage III melanoma, the optimal adjuvant strategy is unknown. In a phase III trial (COMBI-AD) in patients with completely resected, BRAF V600-positive stage III melanoma, the combination of the targeted agents dabrafenib and trametinib improved both five-year relapse-free survival (52 versus 36 percent) and distant metastasis-free survival (65 versus 54 percent) at five years, relative to placebo [4]. Overall survival data are immature. Although these results are promising, we continue to suggest adjuvant anti-PD-1 therapy rather than targeted therapy for most patients with resected BRAF-mutant stage III melanoma, pending further data.


Atezolizumab in PD-L1 high NSCLC

New immunotherapy options are emerging in advanced non-small cell lung cancer (NSCLC). In IMpower 110, in the subset of over 200 patients with advanced NSCLC and PD-L1 expression >=50 percent, atezolizumab improved overall survival relative to platinum based chemotherapy (20 versus 13 months) [5]. Grade >=3 adverse events occurred in approximately 30 percent of patients assigned to atezolizumab and 53 percent assigned to chemotherapy. These results led to approval by the US Food and Drug Administration (FDA) of atezolizumab for the front-line treatment of those with advanced PD-L1 high NSCLC (PD-L1-stained >=50 percent of tumor cells or PD-L1-stained tumor-infiltrating immune cells covering >=10 percent of the tumor area), with no EGFR or ALK genomic alterations [6].


Updated disease-specific prognostic assessment scale for brain metastases

The disease-specific graded prognostic assessment (GPA) for patients with newly diagnosed solid tumor brain metastases has been updated based on data from nearly 7000 patients treated at multiple centers between 2006 and 2017 [7]. Across all major tumor histologies, median survival has improved since the original validation of the GPA a decade ago, now ranging from 8 to 16 months depending on the primary tumor type. Within specific cancer types such as breast cancer, predicted survival ranges from 3 to 36 months depending on the GPA prognostic group. The updated GPA confirms prognostic factors including age, performance status, and extent of extracranial disease, and it incorporates information on genetic changes for which targeted therapies are available. Treatment decisions should incorporate disease-specific prognostic tools such as the updated GPA.


1. Mittendorf EA, Zhang H, Barrios CH, et al. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet 2020; 396:1090.


2. Maubec E, Boubaya M, Petrow P, et al. Phase II Study of Pembrolizumab As First-Line, Single-Drug Therapy for Patients With Unresectable Cutaneous Squamous Cell Carcinomas. J Clin Oncol 2020; 38:3051.


3. Pembrolizumab: US Food and Drug Administration Label. Available at: (Accessed on June 25, 2020).


4. Dummer R, Hauschild A, Santinami M, et al. Five-Year Analysis of Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma. N Engl J Med 2020; 383:1139.


5. Herbst RS, Giaccone G, de Marinis F, et al. Atezolizumab for First-Line Treatment of PD-L1-Selected Patients with NSCLC. N Engl J Med 2020; 383:1328.


6. Atezolizumab injection. United States Prescribing Information. US National Library of Medicine. (Accessed on June 02, 2020).


7. Sperduto PW, Mesko S, Li J, et al. Survival in patients with brain metastases: Summary report on the updated diagnosis-specific graded prognostic assessment and definition of the eligibility quotient. J Clin Oncol 2020; :JCO2001255.


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