Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We report 5-year efficacy and safety outcomes from the phase III KEYNOTE-407 study (ClinicalTrials.gov identifier: NCT02775435 ). Eligible patients with previously untreated, metastatic squamous non–small-cell lung cancer (NSCLC) were randomly assigned 1:1 to pembrolizumab 200 mg or placebo plus carboplatin and paclitaxel/nab-paclitaxel once every 3 weeks for four cycles, followed by pembrolizumab or placebo for up to 35 cycles. Primary end points were overall survival (OS) and progression-free survival (PFS) per RECIST version 1.1 by blinded independent central review (BICR). Five hundred fifty-nine patients were randomly assigned in the intention-to-treat population (pembrolizumab plus chemotherapy, n = 278; placebo plus chemotherapy, n = 281). The median time from random assignment to data cutoff was 56.9 (range, 49.9-66.2) months. OS and PFS were improved with pembrolizumab plus chemotherapy versus placebo plus chemotherapy (hazard ratio [95% CI], 0.71 [0.59 to 0.85] and 0.62 [0.52 to 0.74]), with 5-year OS rates of 18.4% versus 9.7%, respectively. Toxicity was manageable. Among 55 patients who completed 35 cycles of pembrolizumab, the objective response rate was 90.9% and the 3-year OS rate after completion of 35 cycles (approximately 5 years after random assignment) was 69.5%. Pembrolizumab plus chemotherapy maintained an OS and PFS benefit versus placebo plus chemotherapy in previously untreated, metastatic squamous NSCLC and is a standard-of-care first-line treatment option for metastatic squamous NSCLC regardless of programmed death ligand 1 expression.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The phase III, double-blind KEYNOTE-826 trial of pembrolizumab 200 mg or placebo once every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with or without bevacizumab, showed statistically significant survival benefits with the addition of pembrolizumab for patients with persistent, recurrent, or metastatic cervical cancer (primary data cutoff: May 3, 2021). This article reports the protocol-specified final overall survival (OS) results tested in the PD-L1 combined positive score (CPS) ≥1, all-comer, and CPS ≥10 populations. At the final data cutoff (October 3, 2022), the median study follow-up duration was 39.1 months (range, 32.1-46.5 months). In the PD-L1 CPS ≥1 (N = 548), all-comer (N = 617), and CPS ≥10 (N = 317) populations, median OS with pembrolizumab–chemotherapy versus placebo–chemotherapy was 28.6 months versus 16.5 months (hazard ratio [HR] for death, 0.60 [95% CI, 0.49 to 0.74]), 26.4 months versus 16.8 months (HR, 0.63 [95% CI, 0.52 to 0.77]), and 29.6 months versus 17.4 months (HR, 0.58 [95% CI, 0.44 to 0.78]), respectively. The incidence of grade ≥3 adverse events was 82.4% with pembrolizumab–chemotherapy and 75.4% with placebo–chemotherapy. These results show that pembrolizumab plus chemotherapy, with or without bevacizumab, continued to provide clinically meaningful improvements in OS for patients with persistent, recurrent, or metastatic cervical cancer.

PURPOSE: Treatment options are limited for patients with previously treated metastatic colorectal cancer (mCRC). In the LEAP-017 study, we evaluate whether lenvatinib in combination with pembrolizumab improves outcomes compared with standard of care (SOC) in previously treated mismatch repair proficient or not microsatellite instability high (pMMR or not MSI-H) mCRC. METHODS: In this international, multicenter, randomized, controlled, open-label, phase III study, eligible patients age 18 years and older with unresectable, pMMR or not MSI-H mCRC, that had progressed on or after, or could not tolerate, standard treatment, were randomly assigned 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 400 mg intravenously once every 6 weeks or investigator's choice of regorafenib or trifluridine/tipiracil (SOC). Randomization was stratified by presence or absence of liver metastases. The primary end point was overall survival (OS). LEAP-017 is registered at ClinicalTrials.gov ( NCT04776148 ), and has completed recruitment. RESULTS: Between April 8, 2021, and December 21, 2021, 480 patients were randomly assigned to lenvatinib plus pembrolizumab (n = 241) or SOC (n = 239). At final analysis (median follow-up of 18.6 months [IQR, 3.9]), median OS with lenvatinib plus pembrolizumab versus SOC was 9.8 versus 9.3 months (hazard ratio [HR], 0.83 [95% CI, 0.68 to 1.02]; P = .0379; prespecified threshold P = .0214). Grade ≥3 treatment-related adverse events occurred in 58.4% (lenvatinib plus pembrolizumab) versus 42.1% (SOC) of patients. Two participants died due to treatment-related adverse events, both in the lenvatinib plus pembrolizumab arm. CONCLUSION: In patients with pMMR or not MSI-H mCRC that had progressed on previous therapy, there was no statistically significant improvement in OS after lenvatinib plus pembrolizumab treatment versus SOC. No new safety signals were observed.

We aimed to evaluate the association of serum carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA 15-3) levels with clinicopathological parameters in patients with breast cancer (BC) and their efficiency for the prediction of recurrence. The records of 482 female patients with breast cancer diagnosis followed in Medical Oncology and Radiation Oncology clinics of Kartal Dr. Lutfu Kirdar Education and Research Hospital were evaluated retrospectively. The median age of the patients was 49. CEA levels were significantly higher in postmenopausal patients (p = 0.022). There was no association between CEA and CA 15-3 levels and nodal involvement (p = 0.689, 0.379; respectively). CEA levels were significantly higher in hormone receptor-positive patients (p = 0.007). HER2 negative patients had significantly higher levels of CEA and CA 15-3 (p = 0.017 and 0.011, respectively). The evaluation of metastatic patients showed that CEA and CA 15-3 levels before metastasis were significantly elevated (p = 0.016 ve 0.008, respectively). There was no relation between the metastasis site and CEA, CA 15-3 levels (p = 0.936, 0.201, respectively). Receiver operating characteristic (ROC) analysis was performed to determine the role of CEA and CA 15-3 levels in the prediction of metastasis, and cut-off values were 1.39 ng/ml and 14.54 U/ml, respectively. Sensitivities of CA 15-3 and CEA levels were 82.1% and 88.3%; specificities were 47.3% and 46.2%, respectively. CEA and CA 15-3 are useful as tumor markers for early diagnosis of metastases, and their elevations were associated with unfavorable clinicopathological parameters of breast cancer patients. Since these markers are considered a cheap and accessible way of predicting breast cancer prognosis, there is an increasing interest in the prognostic value of serum levels of tumor markers in recent years. More sensitive cut-off values for each marker are needed to be validated with further studies.

Serum leptin level is associated with appetite and energy expenditure in healthy individuals. We aimed to evaluate the serum leptin concentration and the other factors which may be associated with weight loss in patients with advanced gastrointestinal cancer. Forty-four patients with advanced gastrointestinal cancer (25 gastric and 19 colorectal cancer) and 25 healthy controls were enrolled. Serum leptin levels were measured as ng/ml via enzyme linked immuno-sorbent assay (ELISA) method in all subjects. The difference in serum leptin concentration between cancer and control group, the factor associated with its serum level and the relationship between serum leptin concentration and weight loss was evaluated. Serum leptin concentration of cancer group was significantly lower than controls (p = 0.002). Female subjects had significantly higher serum leptin concentration than male subjects in control group (p = 0.01), while not in cancer group (p > 0.05). Serum leptin concentration was significantly related with gender in controls (p = 0.023, β = 0.479), while no gender difference was observed in cancer group (p > 0.05). No relationship was found between serum leptin concentration and weight loss percentage in cancer group in linear regression analysis (p > 0.05). No significant difference was observed in serum leptin concentrations between colon and gastric cancer sub-groups (p > 0.05). Independently from the site of gastrointestinal tract, serum leptin concentration in advanced gastrointestinal cancer is lower than controls and it is not a determinant factor in weight loss. In contrast to healthy subjects, gender does not effect the serum leptin concentration in patients with advanced gastrointestinal cancer.