Immune checkpoint inhibitor (ICI) therapy is currently a standard of care for many malignancies. Recent findings suggest that the outcomes of ICI therapy may be influenced by concomitant medications that also have immunomodulatory properties, such as corticosteroids and antibiotics. Two study teams presented findings that explored the effects of concomitant use of acetaminophen and the live bacterial product CBM588 on ICI efficacy in cancer patients.
Antoine Italiano (Institute Bergonié, France) assessed the impact of acetaminophen use on immunotherapy efficacy in patients with different types of cancer [1]. The study showed that detectable plasma acetaminophen levels at treatment onset were associated with a worse clinical outcome in ICI-treated cancer patients and reduced treatment efficacy. Important unanswered questions remain, including the nature of the influence of the previous acetaminophen exposure, whether there is a difference between sporadic and chronic acetaminophen use, and whether there is any influence of acetaminophen on ICI-related toxicity.
The negative association between ICI response and concomitant antibacterial therapy is well defined. Nazli Diman (City of Hope Comprehensive Cancer Center, California, USA) investigated whether concomitant use of the live bacterial product CBM588 (a probiotic strain of bacteria that can restore species of Bifidobacterium to the microbiome) with ICI therapy could facilitate an improved response [2]. The study enrolled patients with newly diagnosed metastatic renal cell carcinoma and showed that adding CMB588 to the standard treatment scheme with nivolumab/ipilimumab increased the objective response rate from 20% to 58%. The investigators suggested that CBM588 decreases antibiotic resistance, which is significant given the common use of antibiotics in cancer patients to treat infections.
Circulating tumor DNA (ctDNA) was first described in 1948, but the first clinical validation happened only when next-generation sequencing (NGS) technology was introduced in the 2000s [3]. The symposium “ctDNA: Dawn of a New Era” at this year’s meeting discussed how this methodology is transforming the field of oncology.
During the past several years, liquid biopsy (detection of ctDNA through a simple blood draw) has gained much attention in clinical practice and clinical research.
In May 2022, the U.S. Food and Drug Administration (FDA) released industry guidance on ctDNA testing when developing drugs for early-stage tumors [4]. The guidance describes three potential uses for ctDNA:
1. Selecting patients for treatment based on molecular alterations
2. Monitoring tumor response at the molecular level via minimal residual disease to identify risk of recurrence
3. Acting as an early surrogate measure of long-term outcomes
The biggest challenge with ctDNA testing is that researchers still do not know whether intervening after a positive ctDNA result will improve patients’ outcomes like survival or quality of life. Multiple clinical trials aim to address this question, particularly what should be done in the case of a positive (or negative) ctDNA result.
Several studies presented during the 2022 ASCO Annual Meeting focused on ctDNA testing across multiple tumor types, including head and neck cancer, non-small cell lung cancer (NSCLC), breast cancer, soft tissue sarcoma, and oropharyngeal cancer. Based on the findings from these papers, we can conclude that:
The interpretation of ctDNA-negativity must follow the same pattern as for many diagnostic tests — ctDNA-negativity does not mean the disease is cured, but ctDNA-positivity does mean it is not cured.
Approximately 10% of patients had detectable ctDNA; of those, 75% or six patients out of eight developed distant metastatic recurrence.
The CHiRP study presented by Marla Lipsyc-Sharf, MD (Dana-Farber Cancer Institute, Massachusetts, USA) followed patients over five years after diagnosis of high-risk stage II/III hormone receptor–positive, HER2-negative breast cancer [5]. Approximately 10% of patients had detectable ctDNA; of those, 75% or six patients out of eight developed distant metastatic recurrence, with a median time of one year until clinical relapse. The other two patients with detectable ctDNA had not experienced recurrence at the time of the last follow-up visit.
The authors suggest that ctDNA monitoring might offer a feasible and cost-effective option to identify molecular recurrence and allow early treatment intervention. However, the study has certain limitations (small cohort of 83 patients, limited follow-up period, and no surveillance body imaging consistent with current clinical practice). It thus should be considered not as grounds for practice modification but rather as the first step toward understanding the clinical utility of ctDNA in this setting.