The Society for Immunotherapy of Cancer has just issued a detailed statement on the role of immunotherapy in the management of prostate cancer. The full text of this article by McNeel et al. is available on line.
The statement will be of limited assistance to experienced patients since it is highly data focused. Basically, the article
- Reviews the current role of sipuleucel-T/Provenge as a potential agent for the treatment of minimally symptomatic forms of metastatic, castration-resistant prostate cancer (mCRPC)
- Mentions ongoing trials related to the future use of sipuleucel-T in combination with other agents
- Addresses the possible approval of Prostvac VF (rilimogene galvacirepvec/rilimogene glafolivec) if the results of the ongoing Phase III trial of this drug (referred to in the guidelines as PSA-TRICOM), which are expected later this year, are positive
The article does not include any information on the possible use of some of the other, newer forms of immunotherapy (e.g., nivolumab/Opdivo, pemrolizumab/Keytruda, and CAR-T cell therapies) for the simple reason that there are almost no data at all, as yet, to indicate whether such therapies will have real clinical benefit in the treatment of prostate cancer.
On the other hand, the article will be a useful resource for support group leaders and others to be able to make available to patients who are new to the potential value of immunotherapy in the treatment of their disease. Interesting, the article does, very specifically, address the costs of drugs currently available for the treatment of mCRPC.
Filed under: Drugs in development, Living with Prostate Cancer, Management, Treatment | Tagged: guidelines, immunotherapy, Prostvac, Provenge, sipuleucel-T |
THE "NEW" PROSTATE CANCER INFOLINK 
A takeaway from this paper: suggestions for better patient selection for Provenge
Thanks, as always, for your much appreciated work in bringing these papers to the attention of our prostate cancer patient (and I’m sure also physician and researcher) community.
My first impression from this 12-page paper is that the list of authors includes many names of prominent researchers/doctors whom those of us in the active patient community will recognize as leading experts. In fact, Dr. McNeel, the lead author, actually led several of us prostate cancer (and other) survivors on a tour of posters at one of the Scientist Survivor Program sessions sponsored by the American Association for Cancer Research.
To me, from a survivor’s viewpoint, an important takeaway point is that leading experts are homing in on improved patient selection for expensive Provenge therapy ($93,000 for the full course). In brief, pages 5 and 6 mention or discuss these factors that appear to favor longer overall survival after Provenge therapy: lower PSA at the start, no liver metastases, favorable liver enzymes, favorable imaging (rate of growth of the cancer), favorable/acceptable CBC (Complete Blood Count), and generally lower disease burden with disease that is not advancing rapidly. An immune response to Provenge (APCs: Antigen Presenting Cells) is also a good characteristic, but that is not known until after Provenge therapy is started, at least for now, as I understand it.
Many of us have been closely following research with the immune system drug ipilimumab. That is also addressed, with some evidence (of less than top quality) that ipilimumab has some promise in patients with a lower disease burden (like Provenge).
I guess this is the day for immunotherapy reports. Dr. Myers newsletter just arrived; it’s topic this month is immunotherapy.
An Important Feature of Provenge – Much Lower Burden for Side Effects
The panel mentions an important point about Provenge therapy: “… a relative paucity of side effects compared to chemotherapies. …” (p. 8 of 12, in the paragraph on “Cost and value of sipuleucel-T”.
This view of the panel means a lot because of the panel’s view of the timing of the use of Provenge. The panel agreed unanimously that, for appropriate patients (metastatic, castrate-resistant, minimal-to-no-symptoms, sipuleucel-T (Provenge), or abiraterone acetate (Zytiga), or Xtandi (enzalutamide) should be used prior to radium and chemotherapy, with 90% of the panel voting that Provenge be used first. The panel also agreed unanimously that Provenge be used first when it is used, which seems to mean when it is in the program for use for the patient (pages 6 and 7). This means that the patient would be enjoying many months — possibly some years, of a relatively low side effect burden before moving on to more burdensome therapies.
Moreover, based on the rapid rate of progress we are now seeing for late-stage prostate cancer, it seems likely that more attractive options and management know-how for subsequent therapies might emerge during that time.
Problems with Figure 1 — “Prostate Cancer Treatment Algorithm”
I see two flaws in Figure 1.
In the section for “Recurrent ADT Naive” patients, meaning patients who have not yet been on ADT for recurrent disease, only two treatment strategies are listed: first, for non-metastatic patients, clinical trials; second, for metastatic patients, ADT with or without docetaxel (chemotherapy). The glaring omission is ADT/IADT for non-metastatic patients. I’m trying to understand why the panel omitted ADT/IADT for some newly diagnosed patients with localized, but perhaps aggressive, disease. Such use of ADT is common in Japan as I understand it.
The other issue is that, for newly diagnosed patients with localized disease, patients are divided into those getting treatment with curative intent and those treated with non-curative intent, with the stated options being observation and ADT. It may be a small point to some, but using ADT/IADT as treatment deferral strategy to allow technology to improve is another branch of available strategies. That’s exactly what I was hoping for and ultimately did in 2013 after 13 years on ADT/IADT. Granted, these days such an approach is less needed as improvements in imaging, management, and treatments mean patients with challenging cases can more confidently move directly to treatments with curative intent.