Immuno-oncology therapies provided significant potential health gains for both patients and the population, although age should be taken into account to improve accuracy and avoid bias, according to data presented at the virtual 2020 World Conference on Lung Cancer.

“The methods in this study and the inferences taken from this study are positioned to be useful to clinicians and decision-makers in assessing and quantifying the expected survival advantages of [immune-oncology] therapies based on a range of clinically plausible protocols that may be considered in clinical practices,” said Jason Gordon, PhD, technical director of HEOR in Cardiff, United Kingdom, and honorary associate professor at University of Nottingham in the United Kingdom, during the virtual presentation.

Previously, immuno-oncology has been successful in improving responses in overall survival (OS) for small-cell lung cancer. “These novel therapies call for more complicated survival modeling to support the underlying mode of action and clinical plausibility associated with heterogenous response profiles, which are not reflected with standard modeling techniques,” said Gordon during the presentation.

The objective in this comparative approach study was to find the historical age-specific small-cell lung cancer survival rates in the United States and to compare these with expected immuno-oncology survival for a range of durable response rates using mixture cure modeling, which recognizes the mixture of distributions of survival outcomes of patients, said Gordon.

To find historical OS for patients (baseline age, 70 years) with metastatic small-cell lung cancer, researchers used information from the Surveillance Epidemiology and End Results (SEER) database, which was associated with an expected median OS of 5.8 months. Of the patients in this database, approximately 11% survived at 26 months and approximately 5% survived at 60 months.

Data from the CheckMate 032 study were also used, which assessed the effects of nivolumab (Opdivo) and led to a median OS of 4.4 months. Approximately 21% of patients from this study survived at 26 months. They used this study to assume expected outcomes after 26 months, which they projected that 10% of the eligible population would achieve a durable response.

Incremental survival was estimated at a population level by comparing historical outcomes from SEER to long-term survival estimates for patients who received immune-oncology therapy.

“Our results demonstrate there were significant and consistent survival advantages associated [with immune-oncology] treatments compared with historical standards of care,” said Gordon.

Mean OS in patients treated with immuno-oncology treatments was an estimated 29.5 months, with incremental survival gains of 21.2 months. There were significant survival gains across all ages, although more were observed in younger patients compared with older patients.

Researchers used a plausible long-term response fraction for 10% to 100% of survivors (approximately 21% of the study population) at 26 months, which equated to 2.1% to 21% of all patients. When age-adjusted incremental survival estimates were applied to the population with incident small-cell lung cancer (n = 13,570), approximately 27,000 life years were gained with a 10% long-term response fraction, 10,138 life years gained with a 2.1% long-term response fraction and 43,476 life years gained for the 21% long-term response fraction.

“Future research exploring additional data sets, populations and the generalized ability of the study inferences should be considered,” said Gordon.

Gordon J, McEwan P, Kirkness P, et al. Survival in Advanced SCLC: Projected Impact of Immuno-Oncology-Associated Durable Response on Population Health Gains in US. Presented at: 2020 World Conference on Lung Cancer Singapore; January 28-31, 2021; virtual. Abstract FP10.01.

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January 28, 2021 - Immuno-oncology therapies provided significant potential health gains for both patients and the population, although age should be taken into account to improve accuracy and avoid bias.

Immuno-Oncology Therapies Could Be More Beneficiary for Small Cell Lung Cancer

Patients with esophageal/gastroesophageal cancer treated with nivolumab (Opdivo) had improved esophageal-specific and general quality of life, although trends were similar in those treated with placebo, according to data presented at the virtual 2021 ASCO Gastrointestinal Cancers Symposium. 

“It was previously reported that nivolumab is the first adjuvant therapy to provide a statistically significant and clinically meaningful improvement in disease-free survival versus a placebo in resected esophageal cancer/gastroesophageal junction cancer following neoadjuvant therapy,” said Eric Van Cutsem, MD, PhD, professor of internal medicine at the University of Leuven in Belgium and head of digestive oncology at the University Hospital Gasthuisberg in Leuven, during the virtual presentation.

The primary end point of this study was disease-free survival (DFS), with secondary end points of overall survival (OS) and OS rates at 1, 2 and 3 years. Researchers enrolled 794 patients, of whom 532 were randomly assigned nivolumab and 262 randomly assigned placebo.

To assess health-related quality of life, general- and disease-related symptoms, and functioning disease burden, researchers used FACT-E and EQ-5D-3L patient-reported outcome questionnaires. The questionaries were administered at baseline, every 4 weeks during the 12-month treatment, and at post-treatment follow-up visits. Completion rates for patient reports at baseline were 95%, and approximately 90% at 12 months.

At baseline, mean health-related quality of life scores were similar in both groups, and both groups saw an increase in these scores after 1 year.

Scores were similar in the nivolumab and placebo groups for the following: FACT-E total score (133.4 vs. 134.03, respectively), EQ-5D Visual Analogue Scale (70.4 vs. 69.1, respectively) and EQ-5D Utility Index (0.82 vs. 0.831, respectively). Researchers also observed similarities in scores for the esophageal cancer subscale (50.2 vs. 50.1).

Increases in these scores occurred from baseline through most time points through 49 weeks in both groups.

“Patients treated with [nivolumab] did not experience a reduction in [health-related] QoL, further supporting clinical data to demonstrate benefit and tolerability for adjuvant [nivolumab] in patients with resected [esophageal cancer/ gastroesophageal junction cancer],” researchers concluded in the abstract.

Van Cutsem E, Singh P, Cleary JM, et al. Checkmate 577: Health-related quality of life (HRQoL) in a randomized, double-blind phase III study of nivolumab (NIVO) versus placebo (PBO) as adjuvant treatment in patients (pts) with resected esophageal or gastroesophageal junction cancer (EC/GEJC). Presented at: 2021 ASCO Gastrointestinal Cancers Symposium; January 15-17, 2021; virtual. Abstract 167.

January 15, 2021 - Patients with esophageal/gastroesophageal cancer treated with nivolumab had improved esophageal-specific and general quality of life, although trends were similar in those treated with placebo.

Nivolumab Improves Quality of Life in Patients with Esophageal/Gastroesophageal Cancer 

Women who survive breast cancer may have more difficulty in becoming pregnant when compared to the general population, and have a risk of preterm labor, but most deliver healthy babies and experience no detrimental effects on their long-term survival, according to a systematic review and meta-analysis presented at the 2020 San Antonio Breast Cancer Symposium.

“Results of this meta-analysis provide reassuring evidence on the feasibility and safety of conceiving in women with a prior history of breast cancer,” said lead investigator Eva Blondeaux, MD, in a presentation on this data.

Investigators set out to assess the chances of pregnancy in BC survivors compared to the general population and survivors of other cancers, the reproductive outcomes in this population, including complications, delivery outcomes, and fetal outcomes, and to observe maternal safety, in terms of disease-free survival and overall survival. To do so, Blondeaux and her team reviewed the data of 39 studies. A total of 8,265,713 women were included in these studies, with 8,093,401 from the general population. Of the 114,573 BC patients, 7,505 had a pregnancy after diagnosis and 107,068 did not.

When evaluating the chances of pregnancy for breast cancer survivors, Blondeaux and her team compared data from 48,513 BC survivors to those of 3,289,113 women from the general population. A pooled analysis found BC survivors to have significantly lower chances of becoming pregnant when compared to the general population, at about 60% (95% Cl 0.32-0.49); p<0.001). When compared to other cancer survivors, only cervical cancer survivors had a lower chance of becoming pregnant, and overall, all survivors had a lower chance than the general population.

Investigators then compared the data of 3,240 BC patients to 4,814,452 women from the general population to evaluate reproductive outcomes. No differences were found in spontaneous and induced abortion, or pregnancy complications. There was a 14% increased risk for those women who survived BC to undergo a caesarean section, and a 50% higher risk for the child to be low in birth weight.

While BC survivors also had a 45% higher risk of going into preterm labor, the investigators found no significant increased risk of congenital defects or other pregnancy or delivery complications.

In maternal safety, specifically disease-free analysis, 2,003 BC patients with post treatment pregnancy were evaluated, compared to 37,779 BC patients without post-treatment pregnancy. “The results showed no detrimental effect of pregnancy after breast cancer with a hazard ratio (HR) of 0.73, favoring patients with pregnancy after breast cancer,” said Dr. Blondeaux.

In the overall survival analysis, a total of 3,261 BC patients with post treatment pregnancy and 58,238 BC patients without post treatment pregnancy were included. As in the disease-free analysis, no detrimental effect was observed, with a HR of 0.56, also favoring patients with pregnancy after breast cancer.

These findings provide evidence for the feasibility and safety of pregnancy in BC survivors, but as Blondeaux pointed out, the higher risk of fetal complications means those pregnancies to be more closely monitored.

Lastly, Blondeaux noted, the fact that pregnancy appears to have no long-term impact on survivorship highlights the fact that patients’ desires to become pregnant should be considered, as many women can successfully undergo breast cancer treatment and pregnancy to deliver healthy babies.

“The lack of detrimental prognostic effect of pregnancy after breast cancer (irrespective of patient, tumor, treatment, and pregnancy features) strongly voices for the need of deeper consideration of patients pregnancy desire as a crucial component of their survivorship care plan and wish to return to a normal life,” Blondeaux concluded.

December 10, 2020 - Women who survive breast cancer may have more difficulty in becoming pregnant when compared to the general population, and have a risk of preterm labor, but most deliver healthy babies and experience no detrimental effects on their long-term survival.

Colleen Moretti

Articles

Immuno-Oncology Therapies Could Be More Beneficiary for Small Cell Lung Cancer

Nivolumab Improves Quality of Life in Patients with Esophageal/Gastroesophageal Cancer

Pregnancy May Be Difficult for Breast Cancer Survivors, But Often Produces Healthy Babies with No Impact on Long-Term Survival