Transcript:
Anant Ramaswamy, MD: Greetings. My name is Dr. Anant Ramaswamy, and I work at the Tata Memorial Hospital as a medical oncologist. It is an honor to be presenting at the 2020 World GI Cancer Congress.
I will be speaking on an abstract study that we have done which looks at second-line treatment options in advanced gallbladder cancers post-progression on first-line gemcitabine-based regimens.
It's well-known that advanced gallbladder cancers and gallbladder cancers, firstly, are very common in certain parts of India, specifically the Indo-Gangetic Plain, as it's called. While it is not a very common cancer per se, it does have a significant geographical, a high geographical incidence in certain parts of the world.
It is imperative that questions and answers on this particular cancer come from this particular region. World over, first-line treatment for gallbladder cancers is gemcitabine-based regimens, and post-progression, though.
The majority of patients do progress post-first-line treatment. Options are very limited or are not standardized. Approximately five to six years back, a meta-analysis did suggest that chemotherapy might help, but there was not enough evidence to say which chemotherapy and how do we sequence it.
At Tata Memorial Hospital, which is a high-volume cancer center, we get a large number of gallbladder cancer patients who are fit for second-line treatment.
Since we did not have any data per se, prospective data to give a particular regimen at Tata, along with another large center from India called All-India Institute of Medical Sciences, we collaborated to conduct a study.
The study included patients who had progressed on gemcitabine-based regimens and then were randomized to capecitabine plus irinotecan, which was a three-weekly regimen, or monotherapy, irinotecan alone.
There is limited data for both regimens, and we consider this as a trial which would give us answers on whether two drugs was required or single drug was enough for disease control in these patients.
The primary endpoint of our study was overall survival, and at six months, percentage overall survival at six months. The number of patients required for our study was 98 patients, with a one-is-to-one randomized approach.
We started recruiting in July 2018 and completed accrual in Jan 2020. All 98 patients at the end of the study were available for analysis of survival and safety. There were 49 patients in each arm, and with a median follow-up of 5.2 months, 35 patients in the cape-iri arm and 34 patients in the irinotecan arm had died due to disease.
When we look at the primary endpoint of the study, which was overall survival, and our hypothesis was that the doublet regimen would improve survival as compared to monotherapy by approximately 15 percentage points, the overall survival endpoint of cape-iri improving survival over irinotecan was not reached.
The outcomes were similar between both arms. Six-month overall survival for the cape-iri arm was 38 percent, and it was 54 percent for the irinotecan arm, with a P value of 0.93, meaning there was no statistically significantly different survivals between the two groups. This was the primary endpoint of the study.
When we looked at other endpoints like progression-free survival, again, there was no statistically significant difference.
These patients are actually very fragile patients in terms of disease burden, so patient-related quality of life is a very important parameter. Again, there was no difference between the two arms when we evaluated quality of life using the FACT-hep scores. One major difference between, other than the survivals that we saw, is that there were a large number of dose modifications required in the doublet arm.
Almost 27 percent of patients in cape-iri required dose reductions, while only 9 percent of patients required dose reductions in irinotecan. This was statistically significant, with a P value of .016.
The trial has essentially been done in a niche group of patients. That is second-line treatment in gallbladder cancers. While there are now trials in the second-line setting for biliary tract cancers, most of them concentrate, or have a high percentage of, cholangiocarcinomas, unlike our study which was solely done in gallbladder cancer patients.
There is a large study from the UK group which has yet to be fully published, which evaluated a regimen called modified FOLFOX versus only active symptom control. They actually found a benefit for FOLFOX, as compared to active symptom control.
The overall survival in that study for the FOLFOX arm was approximately 6.2 months, which is very similar to what we found in our study. The overall survival for irinotecan in our study was also 6.2 months.
While it is difficult to have cross-trial comparisons, what the available data does suggest is that monotherapy probably is adequate enough as a way forward for advanced gallbladder cancers, and potentially for all biliary tract cancers as well.
Another thing to note is that, while there has been a fair amount of data over the last two years for targeted treatments in cholangiocarcinomas, in gallbladder cancers, unfortunately, we have not been able to identify such targets.
Until the time we identify such targets, chemotherapy is going to be the backbone of treatment for second-line treatment of gallbladder cancers as well. To conclude, I think, this trial shows that, like it or not about the tumors, monotherapy with irinotecan is a good form of treatment as second-line in advanced gallbladder cancers.
It is safe, reasonably efficacious, and does not have too many side effects. If and when targeted treatments also are seen or noted in gallbladder cancer, this will form a good comparator in the future as well.
Before concluding, I'd like to thank our collaborators from the All-India Institute, Dr. Atul Sharma, as well as the members of our gastrointestinal team who were involved in this study, and all the patients who participated in this trial, and allowed us to perform this research.
Also, our funding agencies, who were the Terry Fox Foundation, and our intramural Tata Memorial Hospital funding. With that, thank you.
