Background: We conducted a meta-analysis to evaluate the efficacy and safety of upfront add-on immunotherapy for advanced non-small cell lung cancers (NSCLC). Methods: We performed a literature search on first-line chemotherapy ± immunotherapy in NSCLC. We utilized Revman version 5.3 to calculate the estimated pooled hazard ratio for overall survival (OS) and progression-free survival (PFS) and pooled risk ratio for objective response rate (ORR), all-grade and high-grade adverse events with 95% CI. Results: We analyzed 4322 patients. The pooled hazard ratios for OS, PFS and ORR were 0.74 (95% CI: 0.62–0.88; p = 0.0007), 0.62 (95% CI: 0.57–0.68; p = 0.00001) and 1.51 (95% CI: 1.3–1.74; p = 0.00001), respectively. The pooled risk ratios for all-grade and high-grade adverse events were 1.01 (95% CI: 0.99–1.03; p = 0.27) and 1.17 (95% CI: 1.07–1.28; p = 0.0006), respectively. Conclusion: Add-on immunotherapy significantly improves PFS, OS and ORR for the first-line treatment of advanced NSCLC with a reasonable safety profile.

reports receiving royalties from his book Ending Medical Reversal, that his work is funded by the Laura and John Arnold Foundation, and that he has received honoraria for Grand Rounds/ lectures from several universities, medical centers, and professional societies. Dr Mailankody is a clinical investigator on clinical trials supported by Juno Therapeutics, Janssen Oncology, and Takeda Oncology. No other disclosures are reported.

Background: Ibrutinib targets Bruton’s tyrosine kinase, a kinase involved in signaling of B-cell and chemokine receptors, which are implicated in the pathogenesis of hematologic malignancies. Ibrutinib has been shown to improve survival in hematologic malignancies, and yet the tolerability has not been elucidated. We undertook systematic review and pooled analysis of randomized controlled trials (RTCs) to determine the risk of gastrointestinal toxicities and the rate of treatment discontinuation due to adverse events. Methods: We performed a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts through September 2018. Phase 3 RCTs that mention gastrointestinal toxicities and the rate of treatment discontinuation due to adverse events were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% CI. Random effects model was applied. Results: 6 phase III RCTs with a total of 1,811 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, and Waldenstrom’s macroglobulinemia were included. Studies comparing ibrutinib vs ofatumumab, ibrutinib vs chlorambucil, ibrutinib + bendamustine + rituximab vs placebo + bendamustine + rituximab, ibrutinib vs temsirolimus, and ibrutinib vs rituximab were included in the analysis. The incidence of treatment discontinuation due to adverse events was 9.30% in the ibrutinib group vs 13.13% in the control arm. The relative risk (RR) for treatment discontinuation was 0.740 (95% CI: 0.385–1.423; P=.367). The pooled RR of all-grade side effects were as follows: diarrhea, 1.955 (95% CI: 1.304–2.933; P=.001); nausea, 1.038 (95% CI: 0.702–1.534; P=.852); vomiting, 1.048 (95% CI: 0.547–2.007; P=.888); and stomatitis, 1.262 (95% CI: 0.112–14.173; P=.850). The RR of high-grade adverse effects were as follows: diarrhea, 1.749 (95% CI: 0.866–3.530; P=.119); nausea, 2.237 (95% CI: 0.478–10.471; P=.306); vomiting, 0.429 (95% CI: 0.111–1.659; P=.220); and stomatitis, 0.309 (95% CI: 0.028–3.440; P=.340). Conclusion: Our study demonstrated that patients on ibrutinib arm noted increased risk of all-grade diarrhea. Nevertheless, other GI toxicities as well as treatment discontinuation due to adverse events were not statistically significant in the ibrutinib group compared with the control arm.

Background: Bruton’s tyrosine kinase (BTK) is essential for signaling of B-cell and chemokine receptors. Ibrutinib targets BTK and has become frontier in many hematologic malignancies. We undertook systematic review and pooled analysis of randomized controlled trials (RCTs) to determine the risk of hematologic toxicities and health-related quality of life (HRQOL) events associated with ibrutinib. Methods: We performed a comprehensive literature search using MEDLINE, EMBASE databases, and meeting abstracts through September 2018. Phase III RCTs that mention hematologic toxicities and HRQOL events as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% CI. Random effects model was applied. Results: 6 phase III RCTs with a total of 1,811 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle-cell lymphoma, and Waldenstrom’s macroglobulinemia were eligible. Studies compared Ibrutinib (I) vs ofatumumab, I vs chlorambucil, I+ bendamustine (B) + rituximab (R) vs placebo + B+ R, I vs temsirolimus and I vs R were included in the analysis. The relative risks (RR) of all-grade side effects were as follows: anemia, 0.812 (95% CI: 0.565–1.168; P=.261); neutropenia, 0.956 (95% CI: 0.720–1.268; P=.754); thrombocytopenia, 1.054 (95% CI: 0.450–2.470; P=.904); fatigue, 0.896 (95% CI: 0.761–1.056; P=.192); pyrexia, 1.123 (95% CI: 0.893–1.413; P=.322); and arthralgia, 1.863 (95% CI: 1.101–3.152; P=.020). The RR of high-grade adverse effects were as follows: anemia, 0.522 (95% CI: 0.371–0.733; P<.0001); neutropenia, 0.969 (95% CI: 0.751–1.249; P=.807); thrombocytopenia, 0.608 (95% CI: 0.252–1.470; P=.270); fatigue, 0.618 (95% CI: 0.396–0.964; P=.034); pyrexia, 1.165 (95% CI: 0.534–2.542; P=.701); and arthralgia, 3.623 (95% CI: 0.743–17.663; P=.111). Conclusion: Ibrutinib increased the risk of all-grade arthralgia whereas the risks of high-grade anemia and fatigue were significantly lower in the study arm, favoring ibrutinib.