Evolving Concepts: Immunity in Oncology from Targets to Treatments

Cancer is associated with global immune suppression of the host. Malignancy-induced immune suppressive effect can be circumvented by blocking the immune checkpoint and tip the immune balance in favor of immune stimulation and unleash cytotoxic effects on cancer cells. Human antibodies directed against immune checkpoint proteins: cytotoxic T lymphocytes antigen-4 (CTLA-4) and programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), have shown therapeutic efficacy in advanced melanoma and non-small-cell lung cancer and other malignancies. Immune check point blockade antibodies lead to diminished tolerance to self and enhanced immune ability to recognize and eliminate cancer cells. As a class these agents have immune-related adverse events due to decreased ability of effector immune cells to discriminate between self and non-self. Seventy percent of patients participating in clinical trials have experienced anticancer activities and varying degrees of immune mediated dose-limiting side effects

Exploring causes and consequences of early discontinuation of durvalumab after chemoradiotherapy for non-small cell lung cancer

Introduction: For most locally advanced non–small cell lung cancer (LA-NSCLC) patients who complete definitive chemoradiotherapy (CRT) and do not experience disease progression, one year of adjuvant durvalumab is recommended. Here, we explore causes and consequences of early durvalumab discontinuation. Materials and Methods: We reviewed patients treated for LA-NSCLC with definitive CRT who began adjuvant durvalumab between 2017 and 2021. Duration of durvalumab receipt and causes for early discontinuation were tabulated. Logistic regression models were utilized to evaluate predictors of early durvalumab discontinuation. Landmark analyses were performed to explore associations between early durvalumab discontinuation and clinical outcomes (progression-free survival (PFS), overall survival (OS)). Results: Fifty-nine patients were included. Forty-one patients (69%) discontinued durvalumab early, most commonly for disease progression (n = 14) or lung toxicity (n = 10). Multivariable analysis revealed mean heart radiotherapy dose (MHD) was associated with risk of durvalumab discontinuation from progression (HR = 2.34 per 10 Gy, p = 0.052), and there was a trend suggesting an association between MHD and risk of durvalumab discontinuation from lung toxicity (HR = 2.16 per 10 Gy, p = 0.126). Median PFS duration following durvalumab initiation was 14 months, and median OS duration was 32 months. Landmark analyses that excluded patients with progression or death within one year of durvalumab initiation demonstrated improved outcomes for patients who completed one year of durvalumab (2-year PFS 100% v. 40%, p < 0.001; 2-year OS 100% v. 67%, p = 0.862). Improved outcomes were observed for patients who received MHD below the cohort median (9.3 Gy) compared to patients with higher MHD (median PFS 32 months v. 8 months, p < 0.001; 2-year OS 69% v. 44%, p = 0.088). Conclusion: For LA-NSCLC patients treated with CRT followed by immunotherapy, extent of cardiac irradiation may be a risk factor for immunotherapy discontinuation, disease recurrence, and death

Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer : final analysis of the GioTag study

Aim: Final overall survival (OS) and time on treatment analysis of patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) who received sequential afatinib and osimertinib. Patients & methods: Patients (n = 203) had T790M-positive disease following first-line afatinib and started osimertinib treatment >/=10 months before data entry. Primary outcome was time on treatmentOS analysis was exploratory. Results: Median time on treatment with afatinib and osimertinib was 27.7 months (90% CI: 26.7-29.9). Median OS was 37.6 months (90% CI: 35.5-41.3)median OS was 41.6 and 44.8 months in Del19-positive patients and Asian patients, respectively. Conclusion: In real-world clinical practice, sequential afatinib and osimertinib was associated with encouraging outcomes in patients with EGFR mutation-positive NSCLC, especially in Del19-positive patients and Asian patients

Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer : updated analysis of the observational GioTag study

Aims: Overall survival (OS) and updated time to treatment failure (TTF) analysis of patients with EGFR mutation-positive (Del19, L858R) non-small-cell lung cancer who received sequential afatinib/osimertinib in the real-world GioTag study. Patients & methods: Patients had T790M-positive disease following first-line afatinib and received osimertinib treatment (n = 203). Primary outcome was TTF. The OS analysis was exploratory. Results: Median OS was 41.3 months (90% CI: 36.8-46.3) overall and 45.7 months (90% CI: 45.3-51.5) in patients with Del19-positive tumors (n = 149)2-year survival was 80 and 82%, respectively. Updated median TTF with afatinib and osimertinib was 28.1 months (90% CI: 26.8-30.3). Conclusion: Sequential afatinib/osimertinib was associated with encouraging OS/TTF in patients with EGFR T790M-positive non-small-cell lung cancer, especially in patients with Del19-positive tumors

Sequential treatment with afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer : an observational study

Aim: To assess outcomes in patients with EGFR mutation-positive (Del19, L858R) non-small-cell lung cancer receiving sequential afatinib and osimertinib in a real-world clinical setting. Materials & methods: In this retrospective, observational, multicenter study, patients (n = 204) had T790M-positive disease following first-line afatinib and started osimertinib treatment [>/=]10 months prior to data entry. Primary outcome was time on treatment. Results: Overall median time on treatment was 27.6 months (90% CI: 25.9-31.3), 30.3 months (90% CI: 27.6-44.5) in Del19-positive patients and 46.7 months (90% CI: 26.8-not reached) in Asians. The 2-year overall survival was 78.9%. Conclusion: In real-world clinical practice, sequential afatinib and osimertinib facilitates prolonged, chemotherapy-free treatment in patients with T790M acquired resistance, and is a potentially attractive strategy, especially for Del19-positive tumors

Secondhand Smoke Exposure Among Community-Dwelling Adult Cancer Survivors in the United States: 1999-2012

Little is known about the prevalence of secondhand smoke exposure (SHSe) among cancer survivors. We sought to determine the prevalence, trends, and correlates of SHSe among nonsmoking adult cancer survivors in the United States. Interview and serum cotinine data for nonsmoking adults, age 20 years and older, with a history of cancer ( = 686) were obtained from consecutive two-year cross-sectional cycles of the National Health and Nutrition Examination Survey from 1999 to 2012. SHSe was defined as serum cotinine 0.05-10 ng/mL among nonsmokers. We calculated and trended the prevalence of SHSe among nonsmoking cancer survivors. Multivariable logistic regression was used to examine the associations of SHSe with sociodemographic, smoking, and clinical characteristics. Survey weights were applied in estimating prevalence rates, adjusted ORs, and confidence intervals (CI). The weighted aggregate SHSe and self-reported indoor SHSe prevalence rates over the study period were 28.26% (95% CI: 24.97%-31.55%) and 4.53% (95% CI: 3.48%-5.57%), respectively. SHS exposure declined from 39.61% (95% CI: 27.88%-51.34%) in 1999/2000 to 15.68% (95% CI: 9.38%-21.98%) in 2011/2012 ( \u3c 0.001). Age ≥ 60 years was protective against SHSe, while being black, having less than high school education, poverty, and a smoking-related cancer history were associated with higher odds of SHSe. Fortunately, SHSe among nonsmoking cancer survivors in the United States is on the decline, although certain subgroups remain disproportionately burdened. These findings highlight clinical and public health imperatives to target socioeconomically disadvantaged nonsmoking cancer survivors to reduce their SHSe.