The 2022 annual conference of the American Society of Clinical Oncology (ASCO) was held in Chicago between June 3rd-7th, widely recognised as one of the most important oncology gatherings worldwide and perhaps the most important for clinical research in oncology. Over 40,000 oncology professionals from around the world attended the meeting and over 2,500 abstracts of the latest studies were presented by researchers. Here are what we consider to be the top 3 highlights from the conference.
1. Major breakthrough in breast cancer - progression-free survival (PFS) and overall survival (OS) data on antibody drug conjugate (ADC) trastuzumab deruxtecan (Enhertu®) and expansion of stratification based on HER2 expression
DESTINY-Breast04, is a double-blind, phase III RCT measuring effectiveness of trastuzumab deruxtecan compared to standard chemotherapy. The trial enrolled 557 patients in centres in Asia, Europe, and North America with HR-negative or HR-positive, "HER2-low", unresectable, and/or metastatic breast cancer, who had been previously treated with 1 to 2 prior lines of chemotherapy for metastatic disease.
At a median follow-up time of over 18 months, patients who were HR+ and received trastuzumab deruxtecan had:
- A 49% reduction in risk of the cancer progressing and a 36% reduction in risk of death compared to those who received standard chemotherapy.
- A PFS, of 10.1 months vs. 5.4 months for those who received standard chemotherapy.
- An OS of 23.9 vs. 17.5 months for those who received standard chemotherapy.
The rates of adverse events (AEs) associated with trastuzumab deruxtecan or chemotherapy treatment were similar; however, lung toxicity has emerged as one significant safety concern.In layman terms, these results effectively establish a new "HER2-low" therapeutic subgroup of breast cancer (apart from typically reported HER2-positive and HER2-negative subgroups) and trastuzumab deruxtecan as a standard of care for this subgroup.
Significantly "HER2-low" category can account for as much as 50% of all breast cancers which have been previously clustered with HER2-negative subgroup. This further strenghtens the position of HER2 as a crucial companion diagnostic biomarker in stratification of breast cancer patients.
2. Unprecedented, 100%, response to Tesaro's PD-1 checkpoint inhibitor dostarlimab-gxly (Jesperli®) in dMMR rectal cancer patients
The ongoing interventional, open-label phase II study conducted at Memorial Sloan Kettering will ultimately enroll 30 patients with clinical stage II and III dMMR (DNA mismatch repair-deficient) rectal cancer. Of the 18 patients enrolled to date, most (78%) have T3 or T4 (progressed) rectal tumors. The median age was 54 years, with a range of 26 to 78. All patients had dMMR and BRAF V600E wild-type tumors.
Significantly, the research team has announced at ASCO that it had treated a total of 14 patients with the 6 month treatment regimen by now, and 100% of them have had a clinical complete response (cCR) to dostarlimab-gxly alone. Meaning no patients have required any additional chemotherapy, radiotherapy or surgery to become essentially cancer-free. There have been no disease recurrences observed with the median follow-up of 6.8 months. Four patients have been followed for nearly 2 years, and only four have received less than 6 months of the required treatment.
A companion diagnostic MMR biomarker panel from Roche for dostarlimab-gxly to select for dMMR patient subgroup has been approved by FDA last year.
3. Promising preliminary data from BioNTech’s mRNA cancer vaccine for pancreatic cancer
One of the positive effects of the COVID-19 pandemic has certainly been a rapid adoption of the mRNA technology in the real world, with life-saving mRNA vaccine from BioNTech/Pfizer boasting the first ever COVID-19 vaccine approval. Nevertheless, the real potential of mRNA technology still remains untapped. Pancreatic ductal adenocarcinomas (PDACs) are notoriously hard-to-treat cancers with very low response rates to current types of therapies and, consequently, very high mortality.
At ASCO, the team at BioNTech has presented a preliminary data on the sample of 19 patients from the single-center, interventional, phase I trial evaluating the safety and efficiacy of the treatment of the companies’ mRNA neoantigen vaccine candidate autogene cevumeran in combination with the anti-PDL-1 immune checkpoint inhibitor atezolizumab as an add-on to the standard-of-care regimen with adjuvant chemotherapy in patients with resected PDACs. Autogene cevumeran works by delivering the mRNA for tumour neoantigens to the patient's cells to activate the immune system against the tumour itself.
The data presented at ASCO comprise of the sample of 19 patients after surgery and treatment with atezolizumab. 16 out of these 19 patients (84%) received autogene cevumeran at median point of 9.4 weeks after surgery. The preliminary safety data readout from these 16 vaccinated patients revealed that autogene cevumeran in combination with atezolizumab was well-tolerated with only 1 patient (6%) developing vaccine-related serious AE.
Importantly, the treatment induced de-novo, neoantigen-specific T cell response in 8 (50%) of these patients from undetectable levels to large fractions of all blood T cells with a median fraction of 2.9%. Consequently, at an early median follow-up of 18 months, patients with vaccine-induced immune response (n=8) had a significantly longer recurrence-free survival (RFS) as compared to non-responders (n=8) (median not reached vs. 13.4 months, HR 0.08, 95% CI 0.01-0.4, p= 0.003). Building on these data, an RCT further evaluating the efficiacy and safety is now planned.
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