KEYNOTE B10 Evaluates New Triplet Regimen for Patients With HNSCC

Marcin Dzienis, MD

With the limited available treatment options for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), an ongoing phase 4 trial was developed to evaluate the efficacy and safety of pembrolizumab (Keytruda) combined with carboplatin and paclitaxel in the frontline.

In this open-label, single-arm, phase 4 KEYNOTE B10 trial (NCT04489888), approximately 100 adult patients with a histologically or cytologically-confirmed diagnosis of recurrent/metastatic HNSCC were enrolled and administered pembrolizumab plus carboplatin and paclitaxel.

Patients were given an intravenous (IV) infusion of pembrolizumab at 200 mg on day 1 of each 21-day cycle for up to 35 cycles, carboplatin via IV infusion at area under curve 5 mg/mL/minute on day 1 of each 21-day cycle for up to 6 cycles, and paclitaxel via IV infusion at 100 mg/m2 on day 1 and day 8 of each 21-day cycle for up to 6 cycles or at a dose of 175 mg/m2 on day 1 of each 21-day cycle for up to 6 cycles.

Investigators aimed to assess the primary end point of objective response rate and the secondary end points of duration of response, progression-free survival, overall survival, percentage of patients with adverse events (AEs), and percentage of patients who discontinue treatment on the study due to AEs.

According to Marcin Dzienis, MD, more treatments are needed for patients with HNSCC as it is a difficult-to-treat disease. Despite 5-fluorouracil (5-FU) being associated with unfavorable toxicity, extra costs, and inconvenience, the first-line standard of care strategy for patients with HNSCC has also recently changed and now consists of the combination of pembrolizumab, platinum-based chemotherapy, and 5-FU.

In an interview with Targeted Oncology^TM, Dzienis, medical oncologist, the Gold Coast University Hospital, Queensland Health, further discussed the phase 4 trial of pembrolizumab plus carboplatin and paclitaxel in patients with HNSCC.

Targeted Oncology: What is the standard of care for recurrent/metastatic head and neck squamous cell carcinoma?

Dzienis: The standard of care has recently changed to pembrolizumab, platinum, and 5-fluorouracil based on the data from KEYNOTE-048 study [NCT02358031]. [This trial] investigated it against the previous standard of care which consisted of a platinum, 5-fluorouracil, and cetuximab [Erbitux].

Can you explain the need for new options?

There is a need for new options for patients with metastatic or recurrent head and neck cancer [as patients] have relatively limited treatment options. Many still are unable to have effective treatment options. Also, the choice of therapy is limited based on studies that showed effective results. More than half of the patients do not have effective treatment options to choose from. It is a comorbid patient population with multiple toxicities resulting from previous treatments like surgery, chemotherapy, or radiotherapy. Therefore, a greater choice of treatments based on specific comorbidities may be needed.

What is being investigated in the phase 4 KEYNOTE B10 trial?

The study is a phase 4 single-arm, open-label study to investigate a new combination of paclitaxel, carboplatin and pembrolizumab. The study aimed to assess response rates, survival, and efficacy data. In an early readout looking at safety and response rates alone, we have shown a 42% response rate with this combination. This is slightly numerically higher to what has been previously seen, but overall, it keeps with the triplet therapies used for this patient population. The duration of response was similar to that seen in other studies and the toxicity profile didn't show any surprises or unexpected adverse events. We have seen higher infusion rates secondary to paclitaxel use, but the aim here was to investigate a 5-fluorouracil-free, chemotherapy-based, chemoimmunotherapy.

These findings mostly expand on the available treatment options for patients being treated in the first-line setting. They allow the clinicians and the patients to have an added option which may be more suitable to some patients than an 5-FU-based chemotherapy.

What advice would you give to oncologists who are still using 5-FU? Which patients would you recommend for a different therapy?

5-FU is still a valid treatment option. This study was more to allow clinicians and patients to have access to an added option that may be suitable based on patient preferences or comorbidities. [Overall], this increases options for patients rather than replaces anything we currently have.

5-FU comes with cardiotoxicity and the need for a 4-day infusion, which comes with added costs and complications. Patients willing to avoid those toxicities, as well as those with recent radiotherapy to the oral cavity where they wouldn't be at a higher risk of stomatitis, may prefer to go for paclitaxel. On the other side, patients with neuropathy, for example, may prefer to stick to 5-fluorouracil in place of paclitaxel.

REFERENCE:

​​A study of pembrolizumab (MK-3475) plus carboplatin and paclitaxel as first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (MK-3475-B10/KEYNOTE B10). ClinicalTrials.gov. Updated May 10, 2022. Accessed November 1, 2022. https://clinicaltrials.gov/ct2/show/NCT04489888