Liquid biopsy trial fail

Implosion of Grail’s Galleri Cancer Screening Test?

https://tinyurl.com/3extfeuh

One of the major goals in cancer research is to develop means of early diagnosis for cancers which typically present at an advanced stage, such as ovarian cancer. The Grail cancer screening test is one such attempt. Using circulating tumour DNA as a marker of disease, the test seeks to identify cancer early to improve survival.

This test has been applied over the last three years in the Galleri Clinical Trial in the UK. The prospective trial has 142000 participants aged between 50 and 77, with possible expansion to one million and is administered by the NHS. The key endpoint is reduction in numbers of cancers presenting on diagnosis as stage 3 or 4, with a later stated goal of fewer than 20% of cancers presenting at stage 4. The trial was controversial with complaints of poor use of limited resources and possible bias. However, political pressure in the form of honouring an electoral promise, ensured it’s commencement.

Now the test manufacturer; Grail has announced the preliminary results which show that the primary endpoint has not been achieved. This has caused a collapse in the stock price of the company and led to no further increase in participants for the NHS-sponsored test. The manufacturer claims it is too soon to evaluate the test; numbers of end stage 4 tumour diagnoses are reduced, and survival benefits will take more time to be seen. Of course they would say that wouldn’t they?

New hope for the platinum resistant

FDA approves pembrolizumab with paclitaxel for platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma

https://tinyurl.com/dndxk5ea

Paclitaxel, a combination therapy of a taxane and a platinum drug for chemotherapy of ovarian cancer has been used for more than 30 years. This combination of a cytotoxic and a growth suppressant radically changed the survival for women with this disease.

Unfortunately, drug resistance to this combination especially to the platinum drug is inevitable and for some women this occurs early in the first 6 months after initial treatment, this is known as “platinum resistance”.

Platinum resistance is a grave finding and difficult to treat. Recent results from a clinical trial called KEYNOTE-B96 have shown promising response to a new combination of immunotherapy and chemo using a checkpoint inhibitor (Keytruda) together with paclitaxel with median improved overall survival of 18 months.

Previously immunotherapy with checkpoint inhibitors has not been shown to be effective for high grade serous ovarian cancer. In the context of platinum resistance there is evidence of change in the immune profile with loss of tumour suppression genetic activity and increased circulating programmed cell death protein (PD-1). It is PD-1 which is the marker of checkpoint protection of cancer cells.

Of the 643 patients in the KEYNOTE trial about 70%  were shown to be PD-1 expressers. Severe side effects meant that treatment was terminated early for 16% of those patients who received Keytruda. However, the significantly improved survival for those women in the treatment arm of the trial has prompted FDA approval of the use of Keytruda in combination with Paclitaxel for treatment of platinum resistant ovarian cancer when PD-1 expression is present.

resistant ovarian cancer when PD-1 expression is shown.

Fatal blood clot

Cancer-associated thrombosis in the era of precision oncology: Mechanisms, challenges and future directions

https://tinyurl.com/52e2xt9p

For people with cancer the risk of dying from other causes is increased. The most likely non-cancer cause of death is from thrombosis. Either arterial clot with possible stroke or infarct or venous clot with subsequent pulmonary embolus. Death from thrombosis is up to 12 times more likely for patients with cancer compared to the general population especially early, during chemo.

This review describes why cancer patients are at high risk of thrombosis; it appears there are two groups of cancers those which are at high risk of thrombosis which includes ovarian cancer patients who have a 20% risk, and those which are relatively low risk, breast cancer is in this group.

Thrombosis is a result of slow blood flow, vascular damage or increased clotting factors. Cancer increases all these hazards with some specific issues such as, platelet adhesion and increase in extracellular DNA fibres which act as a focus for blood clot, these are known as neutrophil extracellular traps (NET). As the cancer progresses and spreads the risk of thrombosis is greater.

The presence of venous clot greater decreases the survival of cancer patients. The authors suggest that thrombosis should be anticipated and prophylactic prevention should be routine for cancer patients.

Time toxicity

Health Care Contact Days in Older Adults with Metastatic Cancer

https://tinyurl.com/yjwcbcpn

Sometimes health care professionals forget or fail to recognise the impact a cancer diagnosis can have on the lifestyle of the individual affected. This retrospective study looked at the Medicare reference data for more than 50000 patients with metastatic cancer of varying types, with a comparison of the number of healthcare contact days in 2008 to the same period in 2019.

Findings from the study showed a significant change with the mean number of contact days increasing by about 50% to around 62 days each year. For some cancers, notably breast cancer, the contact days increased even more sharply.

This represents 16% or more of an individual’s already limited life expectancy; this burden on cancer patients has been labelled “time toxicity”. The authors suggest this information should be included in informed consent communication and that attempts to reduce the number of contact days, by arranging same-day appointments would improve the quality of life for cancer patients.