Highlights of 2020 ASCO Annual Meeting
This year the American Society of Clinical Oncology (ASCO) Annual Meeting was delivered in a new virtual format on May 29-31, 2020 with a record-breaking attendance of more than 42,700 participants from 138 countries. The scientific program comprised nearly 5,300 abstracts and more than 100 on-demand and broadcast sessions featuring more than 2,300 oral and poster presentations, a plenary session on the top five practice-changing studies, cancer-specific highlights sessions featuring the highest-impact studies in each area, and clinical cancer symposia.
Here are highlighted several topics including advances in immunotherapies and targeted therapies for different cancers; prevention and improvements in patients’ quality of life, as well as the impact of COVID-19 on people with cancer.
Advances in immunotherapy
Immunotherapy Doubles Time to Disease Progression in Patients With Advanced Colorectal Cancer With Specific DNA Mutations (abstract)
Front-line therapy with the immune checkpoint inhibitor pembrolizumab doubled progression-free survival vs chemotherapy in patients with a type of advanced colorectal cancer that has a high number of mutations, which previous research suggests may have a poor prognosis for some patients. This is the first time pembrolizumab has been shown to benefit these patients when used as a front-line therapy.
Approximately 5% of patients with metastatic colorectal cancer (mCRC) have high microsatellite instability. In these tumors, DNA repair is impaired, resulting in an increased number of mutations. For some patients, previous research suggests that the presence of high levels of mutations in tumors is associated with decreased survival, and patients with microsatellite instability high/mismatch repair deficient (MSI-H/dMMR) metastatic disease are less responsive to conventional chemotherapy.
This phase III KEYNOTE-177 study included 307 patients with MSI-H/dMMR mCRC at the data cutoff for interim analysis. Patients were randomly assigned to receive first-line pembrolizumab for up to 2 years or the investigator’s choice of six different standard chemotherapy regimens, selected prior to randomization.
Previous research has shown good response to pembrolizumab and longer survival for MSI-H mCRC, refractory to chemotherapy. In this study, progression-free survival with first-line pembrolizumab was 16.5 months compared with 8.2 months with chemotherapy with or without targeted therapy, establishing pembrolizumab as the new standard of care for patients with MSI-H/dMMR mCRC.
Severe treatment-related adverse events (grade 3 or greater) were also less common with pembrolizumab than chemotherapy (22% vs. 66%). The profile of toxicities is very different between both groups with immune-mediated adverse events with pembrolizumab (colitis and hepatitis) and classical most frequent chemotherapy toxicities for the chemotherapy arm with diarrhea, neutropenia, fatigue, nausea and vomiting, stomatis, alopecia, and neurotoxicity.
Patients were allowed to cross over at progression from the chemotherapy group to the pembrolizumab group. The study will continue to evaluate overall survival.
Immunotherapy Following Chemotherapy Offers Extended Survival to Patients with Advanced Urothelial Cancer (abstract)
Among 700 randomized patients with advanced urothelial cancer, treatment with avelumab combined with best supportive care following chemotherapy significantly extended overall survival (median 21.4 months) compared with best supportive care alone (median 14.3 months) with hazard ratio [HR] 0.69 (95% CI 0.56, 0.86).
The JAVELIN Bladder 100 phase III study interim results represent the largest survival benefit seen to-date in advanced urothelial cancer in the maintenance setting. While avelumab has already shown efficacy in metastatic disease, this study reports the first data demonstrating efficacy of front-line treatment in the period following initial chemotherapy.
Additionally, avelumab plus best supportive care significantly prolonged overall survival in patients with PD-L1 positive tumors, with median overall survival not yet established. Median overall survival was 17.1 months for this group of patients who received best supportive care alone (HR 0.56; 95% CI 0.40, 0.79). Moreover, in all patients and in those with PD-L1+ tumors, progression-free survival was better with avelumab and best supportive care vs best supportive care alone.
Adverse events of grade 3 or higher occurred in 47.4% of patients who received avelumab plus best supportive care vs 25.2% in those who received best supportive care alone. The most common grade 3 or higher adverse events were urinary tract infection, anemia, hematuria, fatigue, and back pain.
Patients in the control group have been allowed to crossover to the avelumab group. The researchers plan to follow patients to see how long response is maintained.
Immunotherapy Shows Potential in Rare Gynecologic Cancer Resistant to Chemotherapy (abstract)
In a small, phase II study (TROPHIMMUN, cohort A) of gestational trophoblastic tumors, a very rare cancer that develops inside a woman’s uterus during or after pregnancy, treatment with avelumab potentially cured 8 out of 15 women (53%) with cancer that was resistant to single-agent chemotherapy. One patient who was successfully treated with avelumab later went on to have a healthy pregnancy. It was the first report of a normal pregnancy after a curative treatment with an immunotherapy agent.
Avelumab resistance was observed in the remaining seven patients (47%), requiring chemotherapy with/without surgery. Side effects were generally mild, with 93% of patients having grade 1-2 drug-related adverse events (86% grade 1). Fatigue was the most common (33% of patients), followed by nausea and vomiting (33%), and infusion-related reactions (27%).
This is the first trial exploring use of immunotherapy in patients with gestational trophoblastic tumors and suggests that avelumab may be a new therapeutic option for these patients. The researchers are now conducting a similar trial for avelumab in the first-line setting, before resistance to therapy can develop, treating low-risk tumors with methotrexate and avelumab.
Targeted therapy and precision oncology
Post-Surgery Osimertinib Delays Disease Recurrence in Patients With Localized Non-Small Cell Lung Cancer (abstract)
Treatment with targeted therapy osimertinib following surgery for localized non-small cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) mutation significantly improved disease-free survival in a phase III study with 682 randomized patients.
In patients with stage II-IIIA NSCLC who received osimertinib, 90% were alive and disease-free at two years, compared with 44% who received a placebo. The risk of disease recurrence or death was reduced by 83% for patients treated with adjuvant osimertinib after surgery compared to placebo. In the overall population (stage IB-IIIA), treatment with osimertinib reduced the risk of disease recurrence or death by 79% compared to placebo. Disease-free survival at 2 years was 89% with osimertinib compared with 53% with placebo. Overall survival, a secondary endpoint, was immature at the time of data analysis.
The safety profile in this study was consistent with the known safety profile of osimertinib, and the drug was generally tolerable.
Maintenance Therapy With PARP Inhibitor Olaparib Extends Survival By Over 1 Year in Patients With Relapsed Ovarian Cancer and BRCA 1/2 Mutation (abstract)
The unique mechanism of PARP inhibitors highlights the role of targeted therapies for specific gene mutations. BRCA mutations are well-established targets for treatment with PARP inhibitors.
In this double-blind, multicenter randomized phase III SOLO-2 trial, 196 patients with relapsed BRCA-related ovarian cancer responding to platinum-based chemotherapy were randomized to receive olaparib tablets, while 99 received placebo. The patients had also previously received at least two lines of chemotherapy and had cancer that was responding to recent platinum-based chemotherapy.
At 5 years follow up, 42.1% of women receiving olaparib were alive vs. 33.2% on placebo. Olaparib extended overall survival by nearly 12.9 months compared with placebo.
After median follow-up of 65 months, 28.3% of patients who received olaparib were alive and had still not received subsequent treatment, compared with 12.8% of patients who received a placebo. Patients receiving olaparib had a 26% reduced risk of death. In addition, 38.4% of patients in the placebo group crossed over to treatment with olaparib.
Large Scale Precision Medicine Approach Successfully Applied to Pediatric Cancers With Poor Prognosis (abstract)
Researchers have developed an algorithm to identify molecular targets and pair them with targeted therapies for relapsed pediatric cancers with a poor prognosis. In a recent study, this approach extended the time to disease progression by three months for a small group of pediatric patients.
While current treatment of childhood cancers results in high overall cure rates, relapsed high-risk disease is associated with a poor prognosis. For the most part, precision oncology has yet to be applied in pediatric cancer care, unlike in adult cancer where it has improved outcomes.
Among 525 pediatric patients in the INFORM registry from eight countries with a median age of 12 years, 149 patients received targeted treatment based on the targets identified using the algorithm at the discretion of their clinical pediatric oncologist. Of these, 20 had a very high-priority level target – mainly ALK, BRAF, and NRAS mutations and MET and NTRK-fusions. Patients in this group had a median progression-free survival of 204.5 days compared to 114 days for all other 505 patients. There were no clinically relevant differences in overall survival.
The findings show that it is possible to identify precision targets in relapsed pediatric cancers that can guide clinical decision making about treatment approaches. The researchers plan to continue to analyze data from the registry using the algorithm. In addition, based on the results obtained from the INFORM registry, a series of biomarker-driven phase I/II trials (called INFORM2) has been launched.
Prevention and quality of life
Quitting Smoking at Any Point, Even Close to a Lung Cancer Diagnosis, Improves Chances of Survival
People who quit smoking at any time — even less than 2 years before a lung cancer diagnosis — improve their chances of survival after being diagnosed with the disease, according to the results of a large international study.
Tobacco smoking profoundly impacts lung cancer risk. Lung cancer is the leading cause of cancer mortality, making up almost 25% of all cancer deaths, and it is estimated that smoking causes 8 out of 10 lung cancers deaths. While much is known about how smoking cessation affects the risk of developing lung cancer, there has been uncertainty about how soon after smoking cessation survival benefits start to accrue after a lifetime of smoking.
The researchers analyzed data from 17 International Lung Cancer Consortium (ILCCO) studies that included data on time to smoking cessation. This analysis included 35,428 patients with lung cancer, of which 47.5% were current smokers, 30% were former smokers, and 22.5% had never smoked at the time of diagnosis.
Former smokers who quit for less than 2 years before, between 2-5 years before, and for more than 5 years before a lung cancer diagnosis had, respectively, a 12%,16% and 20% reduced risk of death from all causes, when compared to current smokers. Long-term heavy smokers – those who smoked more than 30 pack-years – who quit for less than 2 years before, between 2-5 years before, and for more than 5 years before their lung cancer diagnosis had 14%, 17%, and 22% respective reduced risks of death from all causes, compared to current smokers. This effect was not as strong for those who smoked less than for < 30 pack-years; the reduction rate was significant only for those who had quit at least 5 years before diagnosis (23%).
No matter when smokers quit, their chance of survival increases following a lung cancer diagnosis. The researchers plan to collaborate with local lung cancer screening programs to incorporate the findings from this study into a pilot program of smoking cessation counselling sessions.
Integrating Geriatric Assessment and Management Into Cancer Care Improves Quality of Life, Reduces Hospital Admissions for Older Patients (abstract)
Comprehensive geriatric assessment is a detailed systematic evaluation of an older person that identifies medical, psychosocial, and functional limitations. An integrated approach involving comprehensive geriatric assessment and early geriatrician involvement can help create a coordinated plan to optimize the older person with cancer.
The INTEGERATE trial involved 154 patients with cancer older than 70 years who were going to receive chemotherapy, targeted therapy, or immunotherapy treatment. Patients were randomized to receive integrated oncogeriatric care or usual care.
Patients in the intervention group had significantly better health-related quality of life measured by the validated Elderly Functional Index score than the control group at 12, 18, and 24 weeks. The intervention resulted in improvement in more objective measures as well, including unplanned hospital admissions, and reduced early treatment discontinuation due to adverse events.
The researchers plan to implement an oncogeriatric model of care in a large, multi-center implementation study comparing different care models in geriatric oncology and different cancer settings (e.g. surgical oncology, radiation oncology, inpatient).
The program also featured a session on cancer care in the time of COVID-19.
Data of the Largest Registry of Cancer Patients With COVID-19 (abstract)
According to an analysis of 928 patients with cancer who have tested positive for COVID-19 (around 40% of patients in the registry with active cancer), 13% of patients (121) died within 30 days of COVID-19 diagnosis. After partial adjustment for several baseline factors, patients with progressing cancer were found to be 5.2 times more likely to die within 30 days compared with patients in remission or with no evidence of disease. COVID-19 treatment with both hydroxychloroquine and azithromycin was also strongly associated with increased risk of death, according to data from the COVID-19 and Cancer Consortium (CCC19) registry. Risk of death at 30 days increased nearly two-fold (1.84) with each decade of life. In addition, stable, non-progressing cancer was associated with a 1.79 times greater risk of death than no evidence of disease. Men had a 1.63 times greater risk of 30-day mortality than women. Lastly, former smokers had a 1.6 times greater risk of mortality than non-smokers.
Half of patients included in this analysis (466) were hospitalized following onset of COVID-19. Overall, 14% of all patients were admitted to the intensive care unit. Mechanical ventilation was required for 12% of all patients, and additional oxygen was required by 44% of patients.
The findings could lead to better understanding of the relationship between cancer and COVID-19 to improve care for these patients.
Chemo Within 3 Months of COVID-19 Diagnosis Associated With an Increased Risk of Death in Patients With Thoracic Cancer (abstract)
TERAVOLT registry enrolled over 400 patients with thoracic cancers also diagnosed with COVID-19. Only patients treated with chemotherapy (alone or in combination with other therapies) within 3 months of COVID-19 diagnosis had a significantly increased risk (64%) of dying from the virus compared with patients not receiving chemotherapy. Of the 144 patients who died, 79.4% (112) died due to COVID-19 and 10.6% (15) due to cancer.
Patients with thoracic malignancies, which include lung cancer, mesothelioma, thymic neoplasms, and carcinoid tumors, are considered high risk given their older age, multiple comorbidities and pre-existing lung damage, among other factors.
As more data is collected, findings from the registry are intended to provide insights into the management of patients with both thoracic cancer and COVID-19. Data collection is ongoing, and additional analyses are planned to examine patient and provider perceptions of the impact of COVID-19 on cancer care.