3 early highlights from ESMO 2021

By Michael Woodhead

16 Sep 2021

The European Society for Medical Oncology (ESMO) will hold its annual meeting as a virtual event, the ESMO Congress 2021 on 16-21 September 2021.

Here we present three brief highlights of research findings presented ahead of the meeting.

The limbic will be providing more in-depth coverage of ESMO 2021 next week

CAR T-cell therapies show promise in solid cancers

Dr David Hong

Already established as a treatment for some blood cancers, CAR T-cell therapies are now showing signs of clinical benefit and a manageable toxicity profile in treatment-refractory mesothelin-expressing solid tumours.

Dr David Hong of the University of Texas MD Anderson Cancer Center presented early results from a dose findings study with a novel T-cell receptor fusion construct gavocabtagene autoleucel (gavo-cel; TC-210).

Gavo-cel consists of autologous genetically engineered T-cells expressing a single-domain anti-mesothelin antibody fused to the CD3-epsilon subunit of the T-cell receptor. The construct integrates into endogenous T-cell receptor complexes, allowing HLA-independent T-cell engagement to mesothelin on cancer cells.

The therapy was assessed in a phase I/II trial involving 17 patients (12 with malignant mesothelioma,  four with ovarian cancer and one with cholangiocarcinoma. Patients had received a median of five prior therapies, including immune checkpoint inhibitor and anti-mesothelin therapies.

Following gavo-cel treatment, six out of 16 evaluable patients had ≥30% decrease from baseline in target lesions and the disease control rate was 81%.

The objective response rate was 25%, which included one1 patient with MPM who had a partial response and complete metabolic response by positron emission tomography.

As of the data cut-off date of June 30, 2021, median progression-free survival was 177 days and median overall survival was 337 days.

There were two dose-limiting toxicities (grade 3 pneumonitis at DL1 and haemorrhage at DL5) and six events of grade ≥3 cytokine release syndrome.

Immunotherapy benefit confirmed for MPM

Dr Solange Peters

Long term findings appear to confirm the place of immunotherapy as the first-line therapy of choice in malignant pleural mesothelioma (MPM), according to updated findings from the  CheckMate 743 trial of nivolumab (NIVO) plus ipilimumab.

Dr Solange Peters of Switzerland presented three-year data showing that almost one in four patients with malignant pleural mesothelioma continued to benefit from nivolumab plus ipilimumab.

After a minimum follow-up of 35.5 months and patients being off therapy for one year, the overall survival (OS) rate for nivolumab plus ipilimumab was 1.5-times that of chemotherapy (23.2% versus 15.4%) in patients with unresectable MPM.

Among more than 600 patients, those receiving immunotherapy (n=303) had a 27% reduction in the risk of death compared with those receiving chemotherapy (hazard ratio 0.73).

The overall response rate (ORR) was 39.6% with nivolumab plus ipilimumab and 44.0% with chemotherapy. Exploratory biomarker analysis revealed that a high four-gene inflammatory gene signature score (CD8A, PD-L1, STAT-1, LAG-3) was associated with longer OS in patients receiving immunotherapy but not in those receiving chemotherapy.

Non-oncologists over-pessimistic about cancer prognosis

Dr Conleth Murphy

Doctors working outside of oncology are unaware of the rapid advances attained with immunotherapy and other new treatments, according to researchers whose survey found that patients’ estimated survival times were often underestimated.

In a study conducted in Ireland to assess doctors’ knowledge of current prognoses for different cancers, 301 non-oncology physicians and 46 medical and radiation oncologists were asked to estimate patients’ five-year survival rates for 12 of the most common tumour types across all stages of disease.

The findings showed that non-oncologists underestimated survival of breast cancer, Hodgkin’s lymphoma and renal cancer patients while all groups underestimated survival of people with prostate cancer and melanoma.

When presented with clinical scenarios, non-oncologists were significantly more pessimistic than oncologists on survival of stage 3 colorectal cancer, stage 3 prostate cancer and stage 1 breast cancer patients.

However all groups overestimated the survival of colorectal, lung, liver, gastric and pancreatic cancer.

Dr Conleth Murphy, a co-author of a survey said the findings were important for any physician who discusses a cancer diagnosis and counsels patients.

“Receiving this news is a traumatic experience and patients often immediately have pressing questions about what it means for their future,” he said.

“These results are in line with what we had expected because most physicians’ knowledge of oncology dates back to whatever education they received during their years of training, so their perceptions of cancer prognosis are likely to lag behind the major survival gains achieved in the recent past.”

Dr Murphy recommended that all physicians who routinely interact with cancer patients in their clinic familiarise themselves with the latest statistics and trends in prognosis, while emphasising that non-oncologists should always refrain from answering patients’ questions with numbers.

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