Yang, Fang

Background Invasive micropapillary carcinoma (IMPC) of the breast is associated with a high propensity for lymphovascular invasion and lymph node metastasis. However, whether chemotherapy is associated with improved survival outcomes in these patients remains unclear. Methods This retrospective study analyzed IMPC patients from the SEER database (2010–2018) (n=1,150) and an external validation cohort from Nanjing Drum Tower Hospital (n=199). Propensity score matching assessed chemotherapy’s impact on overall survival (OS) and breast cancer-specific survival (BCSS) in the SEER cohort. A risk stratification model was developed and validated using the external cohort. Results In the SEER cohort, chemotherapy was associated with significantly improved OS (HR = 0.517, 95% CI 0.293-0.910, P = 0.020) but not BCSS. A risk model incorporating marital status, tumor size, subtype, and radiotherapy history identified high- and low-risk groups. Chemotherapy was associated with significantly better OS only for high-risk patients (internal training cohort: HR = 0.577, 95% CI 0.349-0.952, P = 0.029; internal validation cohort: HR = 0.213, 95% CI 0.070-0.647, P = 0.003). External validation consistently confirmed poorer prognosis for high-risk patients (HR = 2.969, 95% CI 1.028-8.571, P = 0.035) and verified the model’s ability to identify patients with differential OS associations with chemotherapy: chemotherapy was associated with better OS in high-risk patients (HR = 0.163, 95% CI 0.031-0.868, P = 0.016), but not in low-risk patients (HR = 0.793, 95% CI 0.153-4.103, P = 0.782). Conclusions Chemotherapy was associated with improved prognosis particularly in high-risk patients with IMPC. However, chemotherapy decisions should be made cautiously for low-risk patients, taking into account a comprehensive assessment of clinical and pathological factors.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) have dramatically changed the landscape of cancer therapy. Both remarkable and durable responses have been observed in patients with melanoma, non-small-cell lung cancer (NSCLC), and other malignancies. However, the PD-1/PD-L1 blockade has demonstrated meaningful clinical responses and benefits in only a subset of patients. In addition, several severe and life-threatening adverse events were observed in these patients. Therefore, the identification of predictive biomarkers is urgently needed to select patients who are more likely to benefit from ICI therapy. PD-L1 expression level is the most commonly used biomarker in clinical practice for PD-1/PD-L1 inhibitors. However, negative PD-L1 expression cannot reliably exclude a response to a PD-1/PD-L1 blockade. Other factors, such as tumor microenvironment and other tumor genomic signatures, appear to impact the response to ICIs. In this review, we examine emerging data for novel biomarkers that may have a predictive value for optimizing the benefit from anti-PD-1/PD-L1 immunotherapy.

7556 Background: The frontline treatment for advanced follicular lymphoma has evolved with the introduction of maintenance therapy, bendamustine (Benda), obinutuzumab (G), and lenalidomide (Len). We conducted a network meta-analysis of phase 3 randomized controlled trials (RCTs) to identify the regimens with superior efficacy. Methods: Data were extracted from 7 RCTs (FOLL05, StiL NHL1, BRIGHT, PRIMA, GALLIUM, StiL NHL7, and RELEVANCE). Progression-free survival (PFS) was compared between 11 regimens with different immunochemotherapy and maintenance strategies. To incorporate direct and indirect comparisons, random-effects Bayesian network meta-analyses were conducted after adjusting for study-wise variation. The posterior inference was derived based on Markov chain Monte Carlo methods and implemented using JAGS v4.3.0. Pairwise comparison of hazard ratios (HRs) and 95% credible intervals (CIs) were calculated. Results: PFS HRs of other regimens compared to the reference regimen are summarized in the Table. Compared to Rituximab(R)-Benda, R-CHOP had inferior PFS, R-CHOP-R, G-CHOP-G, and R-Len-R had similar PFS, while R-Benda-R, R-Benda-R4 and G-Benda-G had better PFS. Compared to R-CHOP-R, G-CHOP-G and R-Len-R had similar PFS, while R-Benda-R, R-Benda-R4 and G-Benda-G had better PFS. In addition, the PFS for G-Benda-G was similar to R-Benda-R4 (HR 0.94, 95% CI 0.78-1.09) but better than R-Benda-R (HR 0.82, 95% CI 0.75-0.97). Conclusions: Compared with the commonly used R-Benda and R-CHOP-R regimens, G-CHOP-G, R-Benda-R and R-Benda-R4 had better PFS, while the chemotherapy-free regimen R-Len-R had similar PFS. [Table: see text]

e20639 Background: Multiple randomized controlled trials (RCTs) have shown a robust benefit of immunotherapy with immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC). We did a meta-analysis to examine the benefit of ICI in various subgroups. Methods: PubMed was searched up to Jan 15, 2019 for RCTs comparing overall survival (OS) between ICI and control (without ICI) arms. Pooled hazard ratio (HR) and 95% confidence interval (CI) was calculated for each subgroup. Interaction tests were done to compare relative benefit between opposed subgroups of interest (eg. men vs women; reported as Pheterogeneity). All analyses were performed with a random effects model in Comprehensive Meta Analysis (v2). Results: Twelve phase 2/3 RCTs involving 7244 patients were included. A significant OS benefit of ICI was found in both squamous and non-squamous histology. Current/former smokers, EGFR wild-type, and KRAS mutant patients had a significant OS benefit from ICI, but never smokers, EGFR mutant, and KRAS wild-type patients did not. An OS benefit of ICI was found in patients with or without baseline brain metastasis, PD-L1 < 1% or ≥1%, men or women, age < 65 or ≥65, and ECOG PS 0 or ≥1. No significant difference of relative benefit from ICI over control was found in patients with different PD-L1 expression, sex, age, or ECOG PS (Table). Conclusions: OS benefit of ICI in NSCLC was associated with a smoking history, wild-type EGFR or KRAS mutation. However, the OS benefit of ICI was seen regardless of histology, PD-L1 expression, sex, age, and ECOG PS. [Table: see text]

6592 Background: Sex, age and ECOG performance status (PS) may affect immune response and the efficacy of cancer immunotherapy with immune checkpoint inhibitors (ICI). We did a meta-analysis to assess the potential sex, age and ECOG PS differences of immunotherapy efficacy in advanced cancer. Methods: PubMed was searched up to January 15, 2019 for randomized controlled trials (RCT) comparing overall survival (OS) in patients with advanced cancer treated with ICI immunotherapy vs control therapy (without ICI). For sex difference analysis, pooled hazard ratio (HR) of death for men and women was calculated separately, and the heterogeneity between the two estimates was assessed using an interaction test by pooling study-specific interaction HR. Age ( < 65 vs ≥65) and ECOG PS (0 vs ≥1) difference was analyzed similarly. Subgroup analysis by cancer type and line of therapy (frontline vs subsequent) was explored. All analyses were done in Comprehensive Meta Analysis (v2) with random effects models. Results: Thirty phase 2/3 RCTs involving 17,728 patients were included. An OS benefit of immunotherapy was found for both men (HR 0.75, 95% confidence interval [CI] 0.69-0.81, P < 0.01) and women (HR 0.79, 95% CI 0.69-0.90, P < 0.01); for both younger ( < 65; HR 0.75, 95% CI 0.68-0.83, P < 0.01) and older (≥65; HR 0.76, 95% CI 0.69-0.83, P < 0.01) patients; and for both ECOG PS 0 (HR 0.78, 95% CI 0.69-0.89, P < 0.01) and PS ≥1 (HR 0.77, 95% CI 0.71-0.84, P < 0.01) patients. No significant difference of relative benefit from immunotherapy over control therapy was found in patients with different sex ( P = 0.283), age ( P = 0.906) or ECOG PS ( P = 0.783). In melanoma RCTs, compared with women (HR 0.77, 95% CI 0.64-0.94, P < 0.01), men (HR 0.56, 95% CI 0.42-0.76, P < 0.01) had more OS benefit from immunotherapy ( P = 0.037). No significant difference was found in other subgroup analyses by cancer types or line of therapy. Conclusions: Overall we found no evidence of association of sex, age, or ECOG PS with cancer immunotherapy efficacy. However, in melanoma, men might benefit more from immunotherapy than women.