Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair-Deficient Colon Cancer.

BACKGROUND: Mismatch repair-deficient (dMMR) tumors can be found in 10 to 15% of patients with nonmetastatic colon cancer. In these patients, the efficacy of chemotherapy is limited. The use of neoadjuvant immunotherapy has shown promising results, but data from studies of this approach are limited. METHODS: We conducted a phase 2 study in which patients with nonmetastatic, locally advanced, previously untreated dMMR colon cancer were treated with neoadjuvant nivolumab plus ipilimumab. The two primary end points were safety, defined by timely surgery (i.e., ≤2-week delay of planned surgery owing to treatment-related toxic events), and 3-year disease-free survival. Secondary end points included pathological response and results of genomic analyses. RESULTS: Of 115 enrolled patients, 113 (98%; 97.5% confidence interval [CI], 93 to 100) underwent timely surgery; 2 patients had surgery delayed by more than 2 weeks. Grade 3 or 4 immune-related adverse events occurred in 5 patients (4%), and none of the patients discontinued treatment because of adverse events. Among the 111 patients included in the efficacy analysis, a pathological response was observed in 109 (98%; 95% CI, 94 to 100), including 105 (95%) with a major pathological response (defined as ≤10% residual viable tumor) and 75 (68%) with a pathological complete response (0% residual viable tumor). With a median follow-up of 26 months (range, 9 to 65), no patients have had recurrence of disease. CONCLUSIONS: In patients with locally advanced dMMR colon cancer, neoadjuvant nivolumab plus ipilimumab had an acceptable safety profile and led to a pathological response in a high proportion of patients. (Funded by Bristol Myers Squibb; NICHE-2 ClinicalTrials.gov number, NCT03026140.).

Characterization of Comments About bioRxiv and medRxiv Preprints.

Importance: Preprints have been increasingly used in biomedical science, and a key feature of many platforms is public commenting. The content of these comments, however, has not been well studied, and it is unclear whether they resemble those found in journal peer review. Objective: To describe the content of comments on the bioRxiv and medRxiv preprint platforms. Design, Setting, and Participants: In this cross-sectional study, preprints posted on the bioRxiv and medRxiv platforms in 2020 were accessed through each platform's application programming interface on March 29, 2021, and a random sample of preprints containing between 1 and 20 comments was evaluated independently by 3 evaluators using an instrument to assess their features and general content. Main Outcome and Measures: The numbers and percentages of comments from authors or nonauthors were assessed, and the comments from nonauthors were assessed for content. These nonauthor comments were assessed to determine whether they included compliments, criticisms, corrections, suggestions, or questions, as well as their topics (eg, relevance, interpretation, and methods). Nonauthor comments were also analyzed to determine whether they included references, provided a summary of the findings, or questioned the preprint's conclusions. Results: Of 52 736 preprints, 3850 (7.3%) received at least 1 comment (mean [SD] follow-up, 7.5 [3.6] months), and the 1921 assessed comments (from 1037 preprints) had a median length of 43 words (range, 1-3172 words). The criticisms, corrections, or suggestions present in 694 of 1125 comments (61.7%) were the most prevalent content, followed by compliments (n = 428 [38.0%]) and questions (n = 393 [35.0%]). Criticisms usually regarded interpretation (n = 286), methodological design (n = 267), and data collection (n = 238), while compliments were mainly about relevance (n = 111) and implications (n = 72). Conclusions and Relevance: In this cross-sectional study of preprint comments, topics commonly associated with journal peer review were frequent. However, only a small percentage of preprints posted on the bioRxiv and medRxiv platforms in 2020 received comments on these platforms. A clearer taxonomy of peer review roles would help to describe whether postpublication peer review fulfills them.