Lots of updates on kidney cancer to report from sessions yesterday. We’re going to do our best to summarize what we learned!
Results of RECORD3 Trial (Which Sequence is Best?)
Large Phase 2 study (that included many Canadian sites) reported on whether it makes any difference to change the usual sequence of the drugs sunitinib (Sutent) and everolimus (Afinitor).
- 238 patients received everolimus followed by sunitinib
- 233 patients received sunitinib followed by everolimus
- total sample included 86% clear cell but almost 15% non-clear cell, primarily papillary
Median PFS (progression free survival) for the first drug was 7.85 months for everolilmus and 10.71 for sunitinib. (Hence, everolimus did not reach its goal of “non-inferiority” as the 1st drug to use).
Approximately 50% of patients moved on to the second half of the study. The sequence of everolimus -> sunitinib yielded a combined PFS of 21.3 months. The sequence of sunitinib->everolimus yielded a combined PFS of 25.79
Net: the standard sequence of sunitinib followed by everolimus continues to be supported.
New Drug: MPDL3280A
This was a Phase 1 trial, so data is still very preliminary. MPD is an engineered PDL1 antibody. Study was to prove safety and tolerability. Drug is IV, every 3 weeks for 1 year, then monitoring. No DLT (dose limiting toxicity) was observed = quite well tolerated. Of 55 RCC patients, 87% were clear cell, 7% were papillary. 13% of patients had a measurable response (shrinkage); 32% patients achieved SD (stable disease). At time of data cut off, all responses were durable/lasting.
- Of those tested for PDL1 over-expression in their rcc tumours, 80% received a benefit (10% complete response).
- However, those proving negative for PDL1 also showed response (though no complete responses)
One challenge is that we don’t know the PDL1 status of the metastases, just of the primary tumour. Additional studies are planned, both as a single agent and in combination with other drugs. Encouraging to see both rapid and gradual responses, as well as prolonged stable disease for patients.
New Drug: Ninetedanib
Tested vs. sunitinib, as first-line drug for mrcc. 64 patients received ninetedanib; 32 received sunitinib. Countries included many in Eastern Europe: Ukraine, Poland, Romania, also the U.K. Unfortunately not many patients in Eastern Europe would have access to a 2nd line drug after this study, so overall survival results would be challenging.
Drug seems similar in side effects to sunitinib, perhaps less hand/foot syndrome but more diarrhea/nausea. Seems not to affect the heart (QT interval). Further studies should be considered if this drug is to be taken further.
– Rencarex vaccine trial (adjuvant use). No clinical benefit was detected as an adjuvant for ALL high risk patients, BUT a biomarker (CAIX) can help select patients who are most likely to respond. (e.g., this treatment requires a companion diagnostic test and would only be given to those patients who could potentially derive a benefit.)
– “delayed nephrectomy” study: first pazopanib, then surgery, then continued pazopanib. 102 patients (PANTHER study). Primary tumour was reduced on avg by 14%. No patient became inoperable as a result of the wait, but only 66% ultimately went on to nephrectomy (patient choice, disease progression, medically not fit). Pazopanib was stopped 2 days before surgery and re-started at least 21 days after surgery. Noted that poor risk patients at the outset did quite poorly.
— future: we are waiting for the GOLD study to report (dovinitinib vs sorafenib) which may lead us to the first drug registered for mrcc in the 3rd line. Would be a new type of drug (FGFR) that may help those who have become refractory (resistant) to other drugs.
Noted that SEQUENCING targeted drugs is required to maximize patient outcomes. We are pushing Overall Survival all of the time to new levels, but we require new drugs to extend survival even further.
Important New Trials for Patients:
- Nivolumab vs everolimus (open across Canada) in the 2nd and 3rd line
- Cabozanitinib vs everolimus (announced just yesterday as opening!)