The ASCO Annual Meeting continues to grow in size and importance and with each year; we see a continued expansion of important clinical research and progress in cancer outcomes. For GI cancers, the 2016 meeting will be remembered for several immediate practice changing results, several thought-provoking and potentially landmark findings, and several highly provocative presentations that will keep us all busy following up on the hypotheses generated. There is no way anyone can consume all ASCO has to offer, even if you narrow it to only one disease, so the reader must be forgiving as I present what I saw as the highlights.
Immune therapy is the hottest thing going and there are two key takeaways regarding immune therapy in colon cancer.
First, all colon patients in all stages must be tested for microsatellite status (MSS or MSI). Not only do we learn if they have the inherited HNPCC syndrome, but now we have solid evidence the checkpoint inhibitors have substantial clinical benefit in these patients with MSI-high metastatic disease. Trials continue to confirm this and I suspect one or more of these agents will be approved in the near future. In the meantime, there are many clinical trial to gain access or through company sponsored access programs. Do this for all your colon patients—especially the metastatic ones.
Second, a small phase III trial (Abstract 3502) showed the combination of cobimetinib and atelzoliumab demonstrated very interesting clinical benefit (both responses and prolonged stable disease) in MSS colon patients. This was a long shot trial based on fairly thin pre-clinical evidence that worked. As a result, a global randomized trial is being initiated. This may be the most important observation presented. Before this, we were close to writing off MSS colon patients as unresponsive to immune therapies. These results open nearly unlimited opportunities for further exploration of combination trials of immune therapy and other agents. While the MSI-high patients represented low-hanging fruit, this study begins the path toward finding the harder to reach, but possibly sweeter, fruit.
Under the heading of “what took us so long,” Drs Venook, Schrag, and Lee presented three abstracts (Abstracts 3504, 3505, 3601) consistently showing that right-sided colon cancers have a worse prognosis than left-sided colon cancers. And the differences are not small. Each reminded us of the long string of prior publications that essentially showed the same thing. So why were these papers recognized as landmark when we already knew this? The major reason is that sidedness may have a therapy impact. The results showed right-sided tumors that were KRAS wt treated with cetuximab did significantly less well than the same group treated with bevacizumab. In contrast, on the left, cetuximab seemed to work better than bevacizumab. Fascinating.
All sorts of theories are being discussed with the leaders such as differences in molecular expression of MSI, BRAF, and others when comparing right and left. Older patients tend to have right-sided cancers. Right-sided tumors are more likely to be found later than left, and others. What do you do with this today? I don't really know. Most agree to not make too many changes until more data comes forward. If there is a change to make, then it would be to avoid front line EGFR therapy in right-sided, and increase use of EGFR therapy in left-sided—of course only in the RAS WT/BRAF WT patients. But I do not think these results say we should never use EGFR in right or VEGF in left. More to come in this space, but make sure you track the side of your patient's tumors and fill out the correct, specific ICD-10 code.
The ESPAC-4 trial compared gemcitabine to gemcitabine plus capecitabine in the adjuvant setting in pancreas cancer (Abstract LBA4006). It was positive, doubling the outcomes for patients with a terrible disease. Not much more to say than this is immediately practice changing. Patients who are currently receiving single agent gem, add cape. Guidelines will change right away. New studies are being proposed looking at this combo with prolonged maintenance cape and others—stay tuned. What remains less clear is the role of radiation, so be cautious in recommending RT.
Finally, the randomized trial testing therapeutic radioactive octreotide (177LuDotatate) was completed and was positive (Abstract e15651). This and similar therapies have been on the horizon for more than a decade and this positive trial should support approval and increased access to this therapy for this increasingly common cancer. A large clinical benefit was observed and safety was high. So your met neuroendocrine patients who are slowly progressing will hopefully have this as a highly effective treatment, possibly before the end of the year.
While not presented at ASCO (but how would you know, you couldn't make it to all the rooms even if you went) an important trial in HCC was presented a couple of weeks later at the ESMO GI meeting in Barcelona. In patients with refractory second line HCC who had progressed on sorafanib, regorafanib demonstrated an OS advantage of about 3 months when compared to placebo. After many years of negative trials, we got a positive one—and an interesting one given sorafanib and regorafanib are very similar compounds, differing by a fluorine molecule. This likely will result in a fairly quick approval for regorafanib in HCC and will add a second tool in the systemic tool box. In addition, there are early but very positive signals for checkpoint inhibitors in HCC which might also enter the toolbox soon. Many reasons to be optimistic for major progress in HCC.
Our biggest challenge going forward is of course paying for all this progress and working to level the inequality of access to cancer care in our neighborhoods and around the world. As ASCO grows, as our clinical research continues to succeed, as we load up the rocket for the moonshot, we cannot forget the value of what we do. As we debate and make hard economically driven healthcare choices going forward, we must always keep our focus on our patients and our quest to cure these terrible diseases.