However, despite mounting evidence that immunotherapies could have long-lasting adverse effects, not all oncologists are convinced that hyperprogression is a real thing. A common argument against hyperprogression is that the observed acceleration in tumor growth could be the natural behavior of an aggressive tumor, not be the result of immunotherapy. Also, the current evidence is retrospectively obtained from clinical trials and data on the rate of tumor growth prior to administration of an immunotherapy are lacking. “Without that initial time point, you can’t separate simple progression from hyperprogression,” Dr Chan said.

“When you don’t have a lot of evidence, it leaves a lot of space for emotional responses,” Hussein Tawbi, MD, PhD, told Cancer Therapy Advisor. Dr Tawbi is the director of melanoma clinical research and early drug development at The University of Texas MD Anderson Cancer Center, Houston. Dr Tawbi is not fully convinced hyperprogression is real based on the current evidence available. He reasons, “I have seen cancer go wild, and I’ve seen it go wild regardless of what treatment you give patients.”

“There is no question that the immune system is a very finely balanced community of cells that interact and have their own checks and balances,” he said. “It is possible that if we push too hard in one spot, the response to this could actually be a complete imbalance and dysregulation that results in the tumor winning over the host. That’s conceivable and possible, but I do think that what would convince me is a mechanistic study in which we actually show that in those patients, here’s what’s happened.”

A recent review article by Champiat and colleagues entertains the possible biological explanations at play among various immune cells, cytokines, and immune-checkpoint molecules, but the explanations are largely rooted in preclinical evidence.2 Individual studies are beginning to emerge that explore the biology of hyperprogressive disease, but the mechanism of how and why it occurs is still unclear.5,8

“More study needs to occur,” Dr Chan asserted. “But I do think it’s real, and so do a lot of other people who have seen it.”

References

  1. Kato S, Goodman A, Walavalkar V, Barkauskas DA, Sharabi A, Kurzrock R. Hyperprogressors after immunotherapy: analysis of genomic alterations associated with accelerated growth rate. Clin Cancer Res. 2017;23(15):4242-4250.
  2. Champiat S, Ferrara R, Massard C, et al. Hyperprogressive disease: recognizing a novel pattern to improve patient management. Nat Rev Clin Oncol. 2018;15:748-762.
  3. Champiat S, Dercle L, Ammari S, et al. Hyperprogressive disease (HPD) is a new pattern of progression in cancer patients treated by anti-PD-1/PD-L1. Clin Cancer Res. 2017;23(8):1920-1928.
  4. Saâda-Bouzid E, Defaucheux C, Karabajakian A, et al. Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Ann Oncol. 2017;28(7):1605-1611.
  5. Lo Russo G, Moro M, Sommariva M, et al. Antibody-Fc/FcR Interaction on macrophages as a mechanism for hyperprogressive disease in non-small cell lung cancer subsequent to PD-1/PD-L1 blockade [published online September 11, 2018]. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-18-1390
  6. Ferrara R, Mezquita L, Texier M, et al. Hyperprogressive disease in patients with advanced non–small cell lung cancer treated with PD-1/PD-L1 inhibitors or with single-agent chemotherapy. JAMA Oncol. 2018;4(11):1543-1552.
  7. Necchi A, Giannatempo P, Raggi D, et al. An open-label randomized phase 2 study of durvalumab alone or in combination with tremelimumab in patients with advanced germ cell tumors (APACHE): results from the first planned interim analysis [published online September 19, 2018]. Eur Urol. doi: 10.1016/j.eururo.2018.09.010
  8. Xiong D, Wang Y, Singavi AK, Mackinnon AC, George B, and You M. Immunogenomic landscape contributes to hyperprogressive disease after anti-PD-1 immunotherapy for cancer. IScience. 2018;9:258-277.