“Now what?” may be the first coherent question a newly diagnosed cancer patient asks. Maybe the smarter version of that is “What–when and why?” And your doctor had better have a good answer, as to the treatment, the when and the why.
We cancer patients usually get surgery “first”, even when the disease has spread. Primary surgical strike and then a clean-up operation, in the ‘war on cancer’ parlance, we think–when we can think. “But which is the best and first clean-up approach?” we must ask. “What works the best? What can I take with my other health problems? Where does surgery or radiation fit in this scheme? What does the doctor favor and why? Where do I get this treatment? And then what?”
Treatments and their sequence are often chosen with little reliance or clarity as to the data. But some light was shed today at ASCO (American Society of Clinical Oncology). It released a comparison of the sequencing of High Dose Interleukin2 (HD IL2) and of targeted therapies for metastatic RCC. Which should come first?
It shouldn’t be a high-stakes gamble to choose a medication, as no one can guarantee any results–with any of the meds. You take a chance with any drug, so which do you start wi We may be closer to a logical approach in sequencing these drugs. Sequencing of these highly different medications has measurable effect on overall survival (OS)—and to patients’ lives. That sequencing is critical and certainly can extend life, even when treatments fail, as they so often do.
A retrospective study of 97 US patients who received HD IL2, before or after a targeted therapy was just presented at ASCO. These patients were followed for a median duration 37 months–half more than 37 months, half fewer than 37 months. Of that group, 22% had either a partial (14%) or complete (8%) response to HD IL2. (No specifics as to what was a “partial” response, perhaps a 30% shrinkage of the total tumor burden). In addition, another 24% of patients had Stable Disease(SD). Thus, nearly half of these patients benefited from having had HD IL2.
Stable disease is better than progressive disease, as any patient knows, though it was rarely measured in older trials. Though we patients really want a cure, we do want to be around for the next treatment, to have a surgery or ablation to remove the “stable” tumor, or to try another medication.
Of these 97 patients, 82 received HD IL2 before any targeted therapy. Another 15 patients had HD IL2 following a TKI therapy. That timing made an important difference. HD IL2 followed by the TKI, showed a median Overall Survival (OS) of 61.8 months. The OS of those with the TKI before the HD IL2 was 48 months. A median, not an average, so half lived longer, half lived shorter than the quoted medians.
A pre-2006 NCI (National Cancer Institute) series showed a 19 month median survival for HD IL2 alone, and a similar 19 months for the use of targeted therapy alone. Using the two in sequence dramatically improved OS, especially when HD IL2 was first line of treatment. Obviously things have improved, though it can be very difficult to compare older trial data, as so many variables are different–including the type of RCC the patients had as they entered the trials.
Several points can be made from this study. First, no therapy should be examined only as to Complete or Partial Response. Stable Disease also adds to Overall Stability. To stop the tumor from growing, even if for a period of time, is valuable to patients and can prep them for the next anticipated treatment. Sure beats tumor growth!
Second, therapies should be chosen to maximize their impact on the overall survival of the patient. Some patients will naturally be precluded (or delayed) from surgery, or taking one drug due to existing co-morbidities, due to heart disease or liver damage. For those post-op patients, likely to tolerate the side effects of HD IL2, it should be given in a first-line setting.
The most critical variables that impact patients are the recommendations and expectations of the physician. Most patients are not even told about HD IL2 treatment, or it is dismissed casually as “not for you”. Others are told to wait until more mets emerge, with some weird theory that waiting for more trouble is a good thing! Many nephrectomy patients are not monitored post-operatively, despite the risk of mets. This is surely an indicator of the lack of knowledge by urologists. Still others are told that the disease has spread, and that nothing can be done–also untrue.
The rarity of RCC and its variants leaves most physicians unaware of all options in the field, and how to any one might suit for a particular patient. Most oncologists to whom patients are referred, have little or no experience treatmenting for RCC, or may not access to academic centers for support until it is too late. Even the pathology of the primary tumor and later metastases may be questionable, adding to the challenge of care.
With the dramatic changes in the RCC field, this is to be expected—but not tolerated. The patient may have to provide his physician with the data that can extend or save his life, which is a sad but realistic commentary on the field today.