Immune Checkpoint Inhibition and Targeted Therapy and Stage IV Melanoma Survival—Reply

In Reply Uno and colleagues highlight a method to quantify the prolongation of survival using the restricted mean survival time (RMST). Based on extracted information from the published survival curves in our article, they estimated that patients in the study cohort (diagnosed 2011-2012) would survive, on average, an additional 2.0 months (95% CI, 1.3-2.7 months) compared with the historical cohort (diagnosed 2004-2008) if followed for 45 months. We used the primary data and computed the difference in RMST to be 2.2 months (95% CI, 1.5-2.9 months) if both groups were followed for 45 months. Uno and colleagues also estimated the difference in median overall survival between the groups to be 1.3 months, which is also accurate; median survival was 6.7 months (95% CI, 6.4-7.0 months) for the historical cohort vs 8.1 months (95% CI, 7.6-8.8 months) for the study cohort, a difference of 1.4 months.

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PIK 3CA Mutations in Hormone Receptor–Positive Breast Cancers

Adjuvant endocrine therapy is recommended to almost every woman with stage I to III breast cancer whose tumor expresses estrogen or progesterone receptors. Several strategies are available to women with early-stage, hormone receptor–positive breast cancer to improve disease-free survival (DFS) and overall survival, including tamoxifen for 5 to 10 years, aromatase inhibitors (AIs) for 5 to 10 years, or a sequential regimen of tamoxifen for 2 to 5 years followed by an AI for 3 or more years. Virtually every study that compared AI-based therapy with tamoxifen has demonstrated small DFS benefits to those receiving an AI. Therefore, the incorporation of an AI as part of their adjuvant endocrine therapy is recommended for postmenopausal women, and premenopausal women with high-risk, hormone receptor–positive tumors are considered for ovarian suppression with an AI.

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Sisu —The Ability to Keep Fighting After Most Would Quit

This article discusses the bravery of an elderly cancer patient from Finland who had sisu, a Finnish word to describe ferocity and tenacity.

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In Search of an Oncogene Driver for Squamous Lung Cancer

Checkpoint inhibitor immunotherapies are playing an increasing role in the therapeutic armamentarium of advanced stage non–small cell lung cancer, regardless of histologic subtype. By contrast, advances in targeted therapy have largely bypassed patients with squamous cell cancers. Identification of new treatable oncogenic drivers has predominately been confined to the nonsquamous subset, or more specifically, adenocarcinoma. The favorable results of tyrosine kinase inhibitor (TKI) therapy among patients whose cancers exhibit these anomalies (eg, alterations in EGFR, ALK, ROS1, BRAF, MET, or RET) have resulted in their inclusion in current guidelines for molecular testing and regulatory approval for associated therapies in most of these genomic subsets. By comparison, no substantial progress has been made in the clinical application of targeted therapy for patients with squamous cancers during this same time, despite the discovery of a number of potential molecular targets and the initiation of associated clinical trials. For example, potentially actionable abnormalities in phosphoinositide 3-kinase (PI3K), cyclin-dependent kinases (CDK) 4/6, and fibroblast growth factor receptor (FGFR) were present in 8%, 19%, and 16% of squamous lung cancers, respectively, in patients screened for the Lung-MAP (S1400) master protocol in advanced squamous lung cancer. Unfortunately, the recently completed Lung-MAP genotype-directed substudies on each of these 3 targets, S1400B (PI3K-directed TKI), S1400C (CDK 4/6-directed TKI), and S1400D (FGFR-directed TKI), failed to reach predetermined efficacy endpoints, with response rates of only 4%, 6%, and 7% and median overall survival of 5.9, 7.2, and 7.5 months, respectively.

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Prevalence of PDL1 Amplification and Preliminary Response to Immune Checkpoint Blockade

This tumor database study examines the prevalence of PDL1 amplification and its utility as a response biomarker to PD-1/PD-L1 blockade in solid tumors.

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Diagnostic Criteria for Noninvasive Follicular Thyroid Neoplasm With Papillarylike Nuclear Features

This review of medical literature examines the criteria for diagnosis of noninvasive follicular thyroid neoplasm with papillarylike nuclear features.

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PD-1 Targeting, Macrophage Infiltration, and IDO Pathway Activation in Patients With Sarcomas—Reply

In Reply We agree with Drs Macciò and Madeddu that a combination of both metronomic chemotherapy and immune checkpoint inhibitors would be a promising approach to improve outcomes of patients with cancer. This is based on the following reasons: (1) Both immune checkpoint inhibitors and metronomic chemotherapy favor immune cell activation. While metronomic chemotherapy can promote tumor-specific immune activation, concomitant administration of immune checkpoint inhibitors may play a crucial role in maintaining the activation status of T lymphocytes. (2) Administration of metronomic chemotherapy would remove metabolic competition between tumor and immune cells. This would facilitate tumor infiltration by cytotoxic immune cells, which has been associated with improved clinical outcome.

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