Docetaxel Added to Radiation Improves Survival in Locally Advanced Head and Neck Squamous Cell Carcinoma

Prof Vijay Maruti Patil, MBBS, MD, DM, Tata Memorial Centre, Mumbai, India, discusses findings from a phase 3 trial that explored the use of docetaxel as a radiosensitizer in patients with head and neck cancer unsuitable for cisplatin-based chemoradiation.

These findings were presented at the 2022 ASCO Annual Meeting.

Transcript:

I'm Dr. Vijay Patil. I'm a professor in the Department of Medical Oncology at Tata Memorial Hospital in Mumbai, India.

At the 2022 ASCO Annual Meeting, we presented an abstract at the head and neck oral session of a phase 3 randomized study, which looked at addition of docetaxel to radiation in cisplatin-ineligible patients.

Whenever we talk about head and neck cancer, we say whether the patient is early stage or locally advanced stage. This abstract pertains to head and neck cancers that are locally advanced. In locally advanced head and neck cancers, either they're managed by surgery, or they're managed by chemotherapy and radiation. Some patients do require radiation after surgery. And along with that radiation, they may or may not require chemotherapy.

Definitive chemoradiotherapy is without doing surgery first. If you require chemotherapy and radiation in order to be given surgery, that is called adjuvant. The best agent to be given with radiation is a drug called cisplatin.

This drug has been available for 3 or 4 decades. It's been proven beyond doubt that this is the best agent. It’s the category 1 recommendation in accordance with the NCCN guidelines. The issue is, around 20 to 30% of the patients are cisplatin-unfit. Then, what to give them is the question. People now extrapolate data from other studies, which were done in cisplatin-fit patients, and try to do cisplatin substitutes, like cetuximab or carboplatin 5-FU, or 5-FU hydroxyurea. The issue with cetuximab is that we don't have very good data that it works in cisplatin-unfit patients. In fact, a study done from our department published in 2011 showed that patients who received cetuximab with radiotherapy and who are unsuitable for platinum don't do well, and they have a lot of side effects.

Secondly, it is very costly. We are in a low- to middle-income country, so less than 1% of my patients can afford cetuximab. The other 2 drugs, carboplatin 5-FU and 5-FU hydroxyurea are, logistically, very difficult to give. They require something called insertion of a line. They require infusions for 4 days. And in India, the incidence of a mutation called DYPD, that is a gene which is required for disruption of 5-FU, is nearly seen in 25% to 28% of the patients. That’s opposed to in the Western world, where it's seen in 1% to 3% of the patients. The side effect rates with these drugs are very high. Hence, most of the oncologists in India would treat these patients with radiotherapy. We decided to see if adding docetaxel to radiotherapy, as compared to radiotherapy alone, could improve the outcomes of these patients.

And this was done in a phase 3 randomized trial with about 356 patients. What we observed was that we had a good mix of both definitive patients, which were treated without doing any surgery, and patients who underwent surgery and then were treated with chemoradiotherapy. And because this was done in India, the predominant cancer is oral cavity. In North America, oropharynx, especially HPV-positive oropharynx is most common. HPV-positive oropharynx in this study was 6% of the patients. Most of these patients tolerated therapy well in both arms, in the radiation arm and the docetaxel radiotherapy arm. More than 90% of the patients in both arms completed their radiation, which means that good quality treatment was received by these patients.

The radiation interruptions were slightly higher in the patients who received docetaxel. It was 11% versus 6% in patients who received only radiotherapy. And the median number of cycles of docetaxel received was around 6, which again is good. Normally 6 to 7 cycles is what the patient needs to get, and they got it.

We found that when we added docetaxel to radiotherapy, it led to a lot of improvement in the disease-free survival. Disease-free survival means that the chances of the disease coming back decreases after we added docetaxel. If you didn't receive docetaxel, the chances that the disease won't come back at 2 years was 30%. If you did receive docetaxel, the chances that the disease won't come back at 2 years was around 42%, so there was a 12% improvement in the chances that the disease won't come back and that were statistically significant. This benefit in disease-free survival was seen across all groups: age, gender, disease stage, end stage or the tumor site of the tumor. It was irrespective of that.

Normally what happens in head and neck cancer is that even if the chances of disease coming back may decrease, it may not add years to life, but the good thing what was observed in the study, lifespan of these patients really increased. The median survival improved from 15 months to around 25 months. At the end of 2 years, 41.7% of patients who received radiotherapy were alive, compared to 50.8% of patients who received docetaxel. And this again was statistically significant.

Did addition of docetaxel lead to increase in side effects? Yes. Addition of any chemotherapy to radiation does lead to an increase in side effects, but these were manageable. Mucositis especially, which is ulcers inside the mouth, increased. And because there were more ulcers inside the mouth, patients had pain inside the throat and mouth, and they had difficulty eating food. And because the intakes were low, a higher proportion of patients had weight loss, but nothing which would be concerning, and this could be easily managed in the hand of an expert medical oncologist and radiation oncologist.

We also looked at quality of life. Overall, there was no difference in quality of life between the 2 arms. Because docetaxel led to an increase in side effect, we were worried that it may lead to a decrease in quality of life of the patients, but that was not so. In fact, what we observed was that decreases in quality of life from the baseline was actually lower in the docetaxel arm. And that was probably because the disease didn't come back in this patient. So they enjoyed their life much better than those patients who received only radiation.

One of the limitation of the studies, is that it was done in India. In the United States and Canada, the patients who had been treated with the radiation with IMRT or 3D-CRT, in India, it's still predominantly 2-dimensional therapy, but even the 2-dimensional is balanced between the arms. It was not that one arm got 2 dimensions. It was balanced between arms, even though IMRT was balanced between the both arms, so that should negate the factors because both arms were comparable in that terms.

Actually we registered around 40,000 patients and around 10,000+ head and neck cancer patients. It is a single-center study, done in a high-volume center. So, it was done by experts in the field, but strength-wise, this is the first study which was done in cisplatin-unsuitable patients. Up until now, no study has been reported with such good positive outcomes.

It did show that docetaxel, which is not necessarily cheap but the cost, in Indian rupees, will cost around 2000 to 3000 while 1 cycle of cetuximab in Indian rupees will cost around 70,000 to 80,000 at present cost. The much difference in the cost is possible, at least in terms of the socioeconomic conditions in this country, with respect to docetaxel. And that's why we concluded in the abstract that this is the best option in cisplatin-unsuitable patients, which can be offered, and it shows that it decreases the chances that the disease would come back, and improves the lifespan of the patients.

Source:

Patil VM, Noronha V, Menon NS, et al. Results of phase 3 randomized trial for use of docetaxel as a radiosensitizer in patients with head and neck cancer unsuitable for cisplatin-based chemoradiation. Presented at: ASCO Annual Meeting; June 3-7, 2022. Chicago, IL, and virtual. Abstract LBA6003.