Alona Zer

Importance: Patients with cancer undergoing treatment are at high risk of COVID-19 following SARS-CoV-2 infection; however, their ability to produce an adequate antibody response to messenger RNA SARS-CoV-2 vaccines is unclear. Objective: To evaluate rates of antispike (anti-S) antibody response to a BNT162b2 vaccine in patients with cancer who are undergoing systemic treatment vs healthy controls. Design, Setting, and Participants: This prospective cohort study included 102 adult patients with solid tumors undergoing active intravenous anticancer treatment and 78 controls who received the second dose of the BNT162b2 vaccine at least 12 days before enrollment. The controls were taken from a convenience sample of the patients' family/caregivers who accompanied them to treatment. The study was conducted between February 22, 2021, and March 15, 2021 at Davidoff Cancer Center at Beilinson Hospital (Petah Tikva, Israel). Interventions: Blood samples were drawn from the study participants. Serum samples were analyzed and the titers of the IgG antibodies against SARS-CoV-2 spike receptor-binding domain were determined using a commercially available immunoassay. Seropositivity was defined as 50 or greater AU/mL. Main Outcomes and Measures: The primary outcome was the rate of seropositivity. Secondary outcomes included comparisons of IgG titers and identifying factors that were associated with seropositivity using univariate/multivariable analyses. Results: The analysis included 180 participants, which comprised 102 patients with cancer (median [interquartile range (IQR)] age, 66 [56-72] years; 58 men [57%]) and 78 healthy controls (median [IQR] age, 62 [49-70] years; 25 men [32%]). The most common tumor type was gastrointestinal (29 [28%]). In the patient group, 92 (90%) were seropositive for SARS-CoV 2 antispike IgG antibodies after the second vaccine dose, whereas in the control group, all were seropositive. The median IgG titer in the patients with cancer was significantly lower than that in the controls (1931 [IQR, 509-4386] AU/mL vs 7160 [IQR, 3129-11 241] AU/mL; P < .001). In a multivariable analysis, the only variable that was significantly associated with lower IgG titers was treatment with chemotherapy plus immunotherapy (β, -3.5; 95% CI, -5.6 to -1.5). Conclusions and Relevance: In this cohort study of patients with cancer who were receiving active systemic therapy, 90% of patients exhibited adequate antibody response to the BNT162b2 vaccine, although their antibody titers were significantly lower than those of healthy controls. Further research into the clinical relevance of lower titers and their durability is required. Nonetheless, the data support vaccinating patients with cancer as a high priority, even during therapy.

8506 Background: The antitumor activity of pembrolizumab, an IgG4 anti-PD-1 monoclonal antibody, was evaluated in patients (pts) with SCLC in KEYNOTE-158 (NCT02628067), a phase 2 basket study of 11 cancer types. Methods: Enrolled pts were aged ≥18 y with advanced SCLC; had measurable disease per RECIST v1.1; ECOG PS ≤1; incurable disease with prior failure of, progression on, or intolerance to standard therapy; and evaluable tumor samples for PD-L1 (PD-L1 IHC 22C3 pharmDx assay [Agilent Technologies]) and other biomarkers. Pembrolizumab 200 mg Q3W was administered for 2 y or until disease progression or intolerable toxicity. The primary endpoint was ORR. DOR, PFS, and OS were secondary endpoints and were estimated by the Kaplan-Meier method. Tumor imaging was performed every 9 wks for the first year, then every 12 wks. Response was assessed per RECIST v1.1 by independent central radiologic review. PD-L1–positive was defined as PD-L1 combined positive score ≥1. Results: Among 107 SCLC pts, median age was 63 y (range, 24–84) and 85 (79%) had 1–2 prior therapies. At the data cutoff date (Aug 23, 2017), 36 pts (34%) were continuing on-study; median follow-up was 10.1 mo (range, 0.5–17.5). Tumors were PD-L1–positive in 42 pts (39%) and PD-L1–negative in 50 (47%); 0 had microsatellite instability-high (MSI-H) tumors and 83 (78%) had microsatellite-stable (MSS) tumors. ORR was 18.7% (20/107; 95% CI, 11.8–27.4) overall, 35.7% (15/42; 95% CI, 21.6–52.0) in pts with PD-L1–positive tumors, and 6.0% (3/50; 95% CI, 1.3–16.5) in pts with PD-L1–negative tumors. Overall, median DOR had not been reached (range, 2.1+ to 13.2+ mo); 12 pts (77%) had DOR ≥9 mo. Median PFS was 2.0 mo (95% CI, 1.9–2.1) in all pts, 2.1 mo (95% CI, 2.0–9.9) in pts with PD-L1–positive tumors, and 1.9 mo (95% CI, 1.6–2.0) in pts with PD-L1–negative tumors. Median OS was 9.1 mo (95% CI, 5.7–14.6) overall, 14.6 mo (5.6–not estimable) in pts with PD-L1–positive tumors, and 7.7 mo (95% CI, 3.9–10.4) in pts with PD-L1–negative tumors. Treatment-related AEs occurred in 63 pts (59%) and led to 4 discontinuations and 1 death (pneumonia). Conclusions: Pembrolizumab has shown promising antitumor activity and durable responses in advanced SCLC, especially in pts with PD-L1–positive tumors. Clinical trial information: NCT02628067.