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Immune Checkpoint Inhibitor- Hyperprogression, Death?

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Immune Checkpoint Inhibitor Hyperprogression, Death?!? Cancer patients only hear about the dramatic success stories of fellow patients who respond remarkably well from ICI’s.

But the research linked and excerpted below talks about a dark side to ICI therapy.

If you asked, say, 100 newly diagnosed cancer patients, most who say that they understand the risk of the chemotherapy regimens that they are about to undergo. Experience has taught me that cancer patients don’t know what they don’t know.

Hyperprogression of ICI therapy is one such example of a possible side effect that conventional oncology probably does not explain to the patient.

I am a long-term cancer survivor who understands the pros and cons, the risks and rewards of conventional cancer therapies such as immune checkpoint inhibitors. My point is that I don’t believe that cancer patients who are considering ICI therapy understand the short, long-term and late stage side effects of conventional therapies.

I don’t believe that newly diagnosed cancer patients understand the difference between the strictly conventional, FDA approved therapy plan presented by their board-certified oncologist or possible complementary therapies that may be available to help treat their cancer. 

Please don’t misunderstand me. I am not anti-conventional oncology. I firmly believe that your oncologist has an important role in managing your cancer. I’m simply saying that conventional oncology is only a small piece of cancer care picture and that, as the article below discuss, there could be serious side effects associated to your FDA approved, “safe and effective” therapies that even your oncologist doesn’t understand.

Are you a newly diagnosed cancer patient? Do you have questions about your symptoms or therapy plan? Scroll down the page, post a question or a comment and I will reply to you ASAP.

Thank you,

David Emerson

  • Cancer Survivor
  • Cancer Coach
  • Director PeopleBeatingCancer

Cancer immunotherapy may have a dark side

“A growing number of fast-progressing cancer cases point to a dark side for so-called checkpoint inhibitors, a type of immune-stimulating drug that has had near-miraculous results in some people with advanced cancer. Only about 20% of patients respond long-term to the drugs, and oncologists are warning that in a few, they may stoke tumor growth.

Despite accumulating papers and anecdotal reports of such tumor “hyperprogression,” some cancer researchers wonder whether it is simply an illusion—whether the patients’ tumors were destined to grow rapidly even before checkpoint inhibitor treatment.

Next week in Atlanta at the annual meeting of the American Association for Cancer Research, researchers will try to resolve how to pin down whether hyperprogression is real and, if so, how to identify which patients should not receive these increasingly popular drugs…”

Hyperprogression as a distinct outcome after immunotherapy.

“Cancer research is living a time of unparalleled expectations around immunotherapy, a therapeutic strategy that materializes the elegant idea of weaponizing our immune system to eradicate tumor cells. In an everchanging standard of care, a growing number of studies have shown that immunotherapy may accelerate tumor progression in a significant subset of patients ranging from 4% to 29% across multiple histologies.

The identification of hyperprogression poses a challenge for RECIST criteria, which fail to capture pre- and post-treatment tumor growth kinetics at early times of disease. To this end, parameters such as the TGR (Tumor Growth Rate), TGK (Tumor Growth Kinetics), and TTF (Time to Treatment Failure) have been proposed.

Although the definition of hyperprogression is not consistent among research groups, it may be depicted as a RECIST progression at the first on-treatment scan with at least a doubling in growth pace when comparing pre- and post-treatment periods.

Unlike pseudoprogression, patients displaying hyperprogression present worse survival outcomes. This phenomenon has been independently associated to older age, higher metastatic load, and previous irradiation, but remarkably failed to show association to tumor burden or aggressive pre-treatment growth.

Despite the pivotal interest of recognizing subjects at increased risk of hyperprogression, only MDM2 amplification and EGFR aberrations have been described as potential biomarkers and require further validation. In addition, tumor mutation burden and circulating DNA may be valuable to this purpose. This work provides an update on epidemiology, clinical predictors, biomarkers, and a plausible molecular rationale of hyperprogressive disease after immunotherapy.”

Early Death May Be Common in Cancer Patients Taking Immune Checkpoint Inhibitors

“Early death may be common among cancer patients taking immune checkpoint inhibitors (ICIs), according to a study published in the Journal of the National Cancer Institute

In a real-world study of more than 7000 cancer patients, 15% had an early death, which was defined as dying within 60 days of starting ICI therapy. Factors such as cancer type, disease stage, and the use of other cancer treatments were associated with the risk of early death…

The study included 7126 patients treated with ICIs from 2012 to 2020. Patients had

  • lung cancer (58.1%),
  • melanoma (23.9%),
  • kidney cancer (10.6%),
  • bladder cancer (4.1%),
  • and head and neck cancer (3.3%). 

A total of 1075 patients (15%) died within 60 days of starting ICI therapy. The ICIs patients received included pembrolizumab (40.3%),

  • nivolumab (37.1%),
  • ipilimumab (6.1%),
  • durvalumab (5.9%),
  • atezolizumab (2.2%),
  • avelumab (0.2%),
  • and a combination of ICIs (8.2%).

An analysis of death at 30 days and 90 days showed similar associations. The death rate was 7% at 30 days and 22% at 90 days.

“Mortality early post initiation of ICI is common in patients with cancer treated with ICI,” the researchers concluded. “Several patient, tumor, and system level factors are associated with EM [early mortality] and need to be prospectively validated to ultimately develop a predictive tool to use in routine practice for better patient selection and treatment guidance…”



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