ASCO20 Virtual Scientific Program Highlights

Welcome to a review of some of the major themes from this year’s ASCO20 Virtual meeting, which just concluded. I have combed through all the presentations to distill some of the major themes of this year’s meeting. This is NOT meant to be a comprehensive review, but rather an outline of four major themes.

·       The role of PARP inhibitors is well established in cancer care, and we know that BRCA mutations confer particular susceptibility to them. Similarly, alterations in other genes  such as those covered under “homologous repair deficiency,” can be of a similar predictive feature

·       Liquid biopsies have become more common in cancer diagnostics, and can the potential role of circulating tumor DNA assays can further be extended to monitor the response to anti-cancer treatments.

· The Use of immuno-oncology agents is gaining popularity and studies about them were quite prominent at the meeting.

·       And finally, the potential for early-stage molecular testing trends for patients with advanced NSCLC at the time of diagnosis.

Identification of PARPi-eligible patients based on BRCA status and HRD score

Today PARP inhibitors are approved for various indications including patients with advanced ovarian, breast, pancreatic, and prostate cancers. The PARP inhibitor landscape is constantly evolving with new clinical trial data emerging rapidly. Below highlighted two abstracts presented at the ASCO20 Virtual Scientific program that suggest how HRD phenotype/high genome-wide LOH can be helpful to select PARPi-sensitive candidates in BRCAwt patients in the ovarian and breast cancer settings.

Veliparib + Cisplatin in gBRCA-negative metastatic TNBC show a trend towards improved overall survival: HRD helped identify 2/3rd of these patients (Abstract #1001) - This is the first randomized study in MBC to show the efficacy of PARPi (veliparib) in combination with platinum chemotherapy in TNBC beyond those with gBRCA mutation. The HRD phenotype was a key factor that helped in the biomarker-guided patient selection for the BRCAwt group to identify PARP-sensitive patients. To summarize, this study suggests that HRD testing can help select BRCAwt patients that may be good candidates for PARPi + platinum chemo combination therapy.

Molecular characterization of long-term responders (DOR ≥ 1 year) to rucaparib include BRCA homozygous deletion/rearrangements and BRCA wild-type with high genome-wide LOH in High-Grade Ovarian Cancer (HGOC) (Abstract #6015)- Molecular characteristics such as BRCA homozygous deletion or rearrangement can be associated with a robust response to rucaparib in HGOC patients when compared to other BRCA mutations. Interestingly, the long-term response can also be observed in BRCAwt patients with high LOH. This data suggests that a high genome-wide LOH can be a predictor of response to rucaparib for BRCAwt patients in ovarian cancer.

Longitudinal Utility of ctDNA Monitoring for Prognosis & Treatment

Repeat tissue biopsy at tumor progression can be challenging to obtain for patients with advanced metastatic disease. Liquid biopsy assays evaluating molecular alterations from circulating tumor DNA (ctDNA) have emerged as a useful rapid, non-invasive tool. The clinical utility of serial monitoring with ctDNA has not been clearly established. Below highlighted are the two abstracts presented at ASCO20 Virtual Scientific program that highlights the potential use of serial ctDNA to determine treatment response in mCRPC patients and to determine resistant alterations in metastatic breast cancer patients.

Circulating tumor DNA (ctDNA) may help inform prognosis, treatment response and survival in patients with mCRPC (Abstract #5508)- Data from this study suggests that ctDNA positivity at baseline is associated with worse rPFS. Additionally, serial monitoring of ctDNA through treatment indicates its potential use as a biomarker for treatment response and an early indicator of disease progression. Further validation of this data in a larger cohort is required to evaluate the clinical utility of serial monitoring via ctDNA in mCRPC patients.

Serial monitoring via circulating tumor DNA (ctDNA) to detect resistance alterations in progressive metastatic breast cancer (Abstract #1084)- Serial monitoring with ctDNA can be a potential tool to monitor progression, identify resistant alterations, and to understand the molecular tumor evolution in metastatic breast cancer patients. Further studies are needed to establish the clinical utility of this tool.

Immunotherapy - Novel Practice-Changing Data in Multiple Tumor Subtypes

Currently, whether to treat patients with first-line immunotherapy with or without chemotherapy is based on clinician discretion, as both are considered standards of care. Several abstracts presented at the ASCO20 Virtual Scientific program have provided clearer evidence on the efficacy of immunotherapy plus/minus chemotherapy in a wide variety of tumor subtypes leading to changes in practice. Interestingly, in several of the studies, PD-L1 negative patients still responded more favorably than the comparator arm of the study.

First-Line Pembrolizumab Plus Etoposide/Platinum for Extensive-Stage Small Cell Lung Cancer (Abstract #9001)- Pembrolizumab plus etoposide/platinum significantly improved PFS and OS adding support to the utility of immunotherapy in the first-line setting for SCLC.

Pembrolizumab monotherapy improves PFS in MSI-H/dMMR metastatic Colorectal Cancer (mCRC) (Abstract #LBA4)- It is critical to test all patients with colorectal cancer for mismatch repair or microsatellite status to assess eligibility for first-line pembrolizumab treatment. OS data is pending.

Avelumab Maintenance Therapy Improves Survival in Advanced Urothelial Cancer (Abstract #LBA1)- Avelumab as first-line maintenance therapy is a new standard of care for patients with advanced urothelial cancers who have not progressed on platinum-based induction therapy.

First-Line Pembrolizumab Plus Chemotherapy Improved PFS in PD-L1–Positive mTNBC (Abstract #1000)- These findings suggest a role for the addition of pembrolizumab to standard chemotherapy for the first-line treatment of metastatic TNBC, especially in PD-L1+ patients. OS follow-up is ongoing.

Molecularly Targeted Treatment in Early-Stage NSCLC Disease

Adjuvant chemotherapy is standard of care in patients with stage II to IIIA NSCLC who have undergone complete tumor resection and select patients with stage IB disease; however, outcomes need to be improved as the 5-year overall survival (OS) benefit with chemotherapy is 5%. In patients with stage IB, II, and III diseases, the 5-year recurrence rates are 45%, 62%, and 76%, respectively

Adjuvant Osimertinib in Early-Stage NSCLC Improves PFS in EGFR+ NSCLC (Abstract #LBA5)- The ADAURA trial assessed adjuvant Osimertinib treatment in EGFR+ NSCLC. Patients received treatment for 3 years, or until disease recurrence or discontinuation criteria were met