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Immunotherapy, Hyperprogressive Disease & Lung Cancer

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The therapy backfires in a newly defined subset of lung cancer patients who experience accelerated tumor growth indicative of hyperprogressive disease 

All toxic therapies have short, long-term and late stage side effects. Anti-PD-1/PD-L1 immunotherapy is no different. Though hyperprogressive disease can happen with other chemotherapy regimens such as sorafenib and crizotinib, what is remarkable is the degree of HPD in NSCLC that resulted from anti-PD-1/PD-L1 immunotherapy. As the study below cites ” In a multicenter study involving 242 patients, 16 percent were identified as having HPD ().”

16% for a single side effect, especially a side effect that means a shorter remission  (progression-free survival) and shorter life (overall survival), is remarkable. Especially when a lung cancer patient considers that there are many other side-effects to consider on top of the cost of anti-PD-1/PD-L1 immunotherapy.

There is no question that immunotherapy can provide remarkable remissions for a small number of cancer patients. The issue then, must be to analyze the risks and benefits of this high risk, high reward cancer therapy.

Or to put it another way, is there a better option? Are there evidence-based therapies that provide a longer length of life and a higher quality of life than Anti-PD-1/PD-L1 immunotherapy?

I think there is. I am a long-term cancer survivor of a different but also incurable cancer called multiple myeloma. Extensive conventional therapies, from surgery to a bone marrow transplant to radiation did little to help me and these therapies did a lot to hurt me. After remission, relapse, remission and relapse, what finally put me into complete remission for the next 20 years was an evidence-based but non-conventional, non-toxic therapy.

In addition to managing PeopleBeatingCancer, a 501c3 non-profit, I am a cancer coach. I work with patient and caregivers to navigate the complicated world of conventional FDA approved therapies as well as the risks and rewards of evidence-based complementary and integrative therapies.

To learn more about evidence-based therapies for lung cancer, please watch the short video below:


Have you been diagnosed with non-small cell lung cancer? Would you like some help understanding all of your therapy options? Please scroll down the page, post a question or comment and I will reply to you ASAP.

Thanks and hang in there,

David Emerson

  • Cancer Survivor
  • Cancer Coach
  • Director PeopleBeatingCancer

Recommended Reading:

Study Finds Hyperprogression After Immunotherapy in NSCLC Subset

“Although anti-PD-1/PD-L1 immunotherapy has greatly improved the treatment of patients with non–small cell lung cancer (NSCLC) and is generally well-tolerated, the therapy backfires in a newly defined subset of patients who experience accelerated tumor growth indicative of hyperprogressive disease (HPD), according to research presented at the 2017 ESMO Congress.

A multicenter retrospective analysis of patients with NSCLC treated with the checkpoint blockade antibodies determined that 16% had HPD, which negatively affected their overall survival (OS) and progression-free survival (PFS) compared with patients without HPD. The study examined results for 242 patients treated in 5 institutions in France between November 2012 and March 2017…

“The incidence of HPD is about 9% in cancer patients overall,” said lead study author Roberto Ferrara, MD, in an interview with OncLive. “Immunotherapy makes the tumors grow faster in a subset of patients; we need to know the biology behind this to identify the patients at risk for HPD…”

HPD is more rapid than typical disease progression and has an impact on OS, investigators found. In this study, patients with HPD had a median OS of 3.3 months while those with progression according to RECIST criteria had median OS of 5.7 months…

Similarly, patients with HPD experienced significantly shorter median PFS of 1.4 months compared with 4.9 months for the not-HPD population: median OS was also shorter at 3.3 versus 17 months, respectively, for the 2 cohorts…

“Further work is needed to better characterize the population of patients at risk of HPD,” said Ferrara…”

Hyperprogressive disease in patients with non-small cell lung cancer on immunotherapy

“Immunotherapy agents in metastatic non-small cell lung cancer (NSCLC) can result in improved quality of life and survival when compared with platinum-based chemotherapy. Novel response patterns such as pseudoprogression and hyperprogression, however, have been described and pose a challenge to treating physicians…

Hyperprogressive disease (HPD)

Some patients on immunotherapy may experience a rapid paradoxical progression of tumor with worsening clinical status, which appears to negatively impact survival (,,). This phenomenon has been termed HPD. Until recently, only anecdotal reports existed describing clinical and radiographic deterioration after initiation of immunotherapy, but the prevalence, natural history, and predictive factors were unknown (,)…

A study of 131 patients with various tumor types from five French hospitals identified 9 percent of patients as having HPD after treatment with anti-PD-1/PD-L1 mAbs ()…

Emerging data show that in NSCLC the rate of HPD may be even higher. In a multicenter study involving 242 patients, 16 percent were identified as having HPD (). These patients had significantly lower median progression free survival (1.4 vs. 4.9 months) when compared with patients without HPD. There was no significant difference in terms of tumor burden at baseline, clinical, molecular, or pathological characteristics, PD-L1 expression status, or response rate to treatment before the introduction of immunotherapy…”

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