New research was virtually presented at ESMO 2021, the European Society for Medical Oncology Virtual Congress 2021, from September 16-21. The features below highlight some of the studies that emerged from the conference.

Adequate Immune Response With COVID-19 Vaccine in Patients on Chemo- or Immunotherapy

Although vaccination against SARS-CoV-2 is recommended for patients with cancer, the impacts of chemotherapy and immunotherapy on immunogenicity and safety is still unclear. Researchers who assessed the impact of immunotherapy, chemotherapy, and chemo-immunotherapy on immunogenicity and safety of COVID-19 vaccination in patients treated for a solid tumor compared the primary endpoint of SARS-CoV-2 Spike S1-specific IgG serum antibody response, defined as >10 binding antibody units (BAU)/ mL 28 days after the second vaccination among individuals without cancer (A) and patients with solid tumors who were treated with immunotherapy (B), chemotherapy (C), or chemo-immunotherapy (D). The primary endpoint was achieved in 100%, 99.3%, 97.4%, and 100% of the participants in cohorts A, B, C, and D, respectively. The antibody response was considered adequate after the first vaccination in 66.0%, 37.1%, 32.5%, and 33.3% of the participants in cohorts A, B, C, and D, respectively. At 28 days after the second vaccination, this increased respectively to 99.6%, 93.1%, 83.8%, and 88.8%. Moreover, spike-specific T cell responses were detected in 46.7% of suboptimal and non-responders. No new safety signals were observed.

Intensified Hormone Treatment Benefits Men With High-Risk, Non-Metastatic Prostate Cancer
Although studies indicate that treatment with androgen deprivation therapy for 3 years and local radiotherapy has improved outcomes of patients with high-risk, non-metastatic (M0) prostate cancer, post-treatment failure rates are high. In patients with metastatic prostate cancer, the addition of abiraterone acetate plus prednisolone (AAP) to androgen deprivation therapy (ADT) has been shown to increase overall survival (OS). However, due to low numbers of events, no statistically significant benefit of adding AAP to ADT was shown in patients with M0 prostate cancer. To compare metastasis-free survival (MFS) in M0 patients, investigators randomized nearly 2,000 men with M0 prostate cancer to ADT plus AAP (or ADT plus AAP plus enzalutamide) or ADT alone. APP-based therapy improved MFS (180 vs 306 events; HR, 0.53). The addition of AAP (± enzalutamide) to ADT improved MFS at 6-year follow-up from 69% to 82%. There was no difference observed between benefit from combining AAP with ADT or combining AAP plus enzalutamide with ADT (HRs, 0.54 and 0.53, respectively). In addition, OS was improved by combining AAP (± enzalutamide) with ADT. Six-year OS rates improved from 77% to 86%; 6-year prostate cancer-specific survival improved from 85% to 93%.

No Survival Impact With Drug-Free Interval in TKI-Therapy for Renal Cell Carcinoma

With increasing interest in the use of treatment breaks with tyrosine kinase inhibitors (TKIs) to reduce toxicity without compromising efficacy, researchers sought to determine if a TKI drugfree interval strategy (DFIS) was non-inferior to a conventional continuation strategy (CCS) in the first-line treatment of advanced renal cell carcinoma (RCC). After 24 weeks of treatment, DFIS patients took a treatment break until disease progression, with additional breaks dependent on disease response and patient/clinician choice. Trial strategy continued until intolerance, progression on treatment, or death. At least one treatment break was mandated, with a median treatment break length of 87 days. Outcomes were overall survival (OS) and Quality Adjusted Life Years (QALYs). Both co-primary endpoints had to demonstrate pre-defined non-inferiority (≤7.5% for OS; ≤10% for QALYs) in intention-to-treat (ITT) and per-protocol (PP) analyses for non-inferiority to be concluded. For OS, there was a difference in conclusion precluding confirmation of non-inferiority. In the ITT population, the HR was 0.97, whereas in the PP population, the HR was 0.94, meaning DFIS in the PP population could not be regarded as non-inferior to CCS. However, consistent non-inferiority in the both the ITT and PP population was demonstrated for QALYs. In addition, both time to strategy failure and summative progression-free interval showed significant differences in favor of the DFIS arm. Also, at 2 years, DFIS was associated with cost savings.

Gut Microbiota Predicts Solid Tumor Immunotherapy Outcomes

Immune checkpoint inhibitors (ICIs) have shown promising anti-tumor activity in a variety of cancer types, and gut microbiota have been shown to modulate efficacy of ICIs. In addition, the diversity of the gut microbiome is regarded as predictive for favorable responses to ICIs. A nationwide cancer genome-screening project that prospectively assessed gut microbiota and circulating tumor DNA (ctDNA) in 2,000 patients with advanced solid tumors was conducted for assessing the alpha diversity index (ADI) of the fecal microbiome, represented as an operational taxonomic unit (OTU) score (OTU-high was defined as a score >240). Among participants, 81% received ICI alone and 19% received ICI and chemotherapy combination. The overall response rate (ORR) in OTU-high patients was 35%, while that in OTU-low patients was 17%. Microsatellite instability, blood tumor mutational burden (TMB), and tissue TMB status were not associated with ORR. OTU-high patients had a significantly longer progression-free survival on ICIs than did OTU-low patients (8.6 vs 2.6 months).

Progression-Free Survival Tripled in DESTINY-Breast03

The global head-to-head, open-label, randomized, phase 3 DESTINY-Breast03 study evaluated the safety and efficacy of trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2-positive unresectable and/ or metastatic breast cancer previously treated with trastuzumab and a taxane. After 15.5 and 13.9 months of follow-up in the T-DXd and T-DM1 arms respectively, blinded independent central review determined that the median progression free survival (PFS) for patients treated with T-DXd was not reached compared with 6.8 months for T-DM1 (HR, 0.28). Patients treated with T-DXd experienced a threefold improvement in PFS of 25.1 months vs 7.2 months with T-DM1 (HR, 0.26). PFS benefit was consistent across key subgroups of patients treated with T-DXd, including those with a history of stable brain metastases. Differences in estimated 12- month OS (94.1% with T-DXd vs 85.9% with T-DM1) did not cross the pre-specified boundary for significance (HR, 0.56) but showed a strong interim trend. The safety profile of the most common adverse events with T-DXd in DESTINYBreast03 was consistent with previous data and no new safety concerns were reported.