PBS, Keytruda and NSCLC...., page-7

Treatment with Keytruda (pembrolizumab) extends in clinically meaningful ways the lives of people with recurrent or metastatic head and neck squamous cell carcinoma (SCC) compared to standard treatment, especially those whose tumors express PD-L1, data from a Phase 3 trial show.

The findings, “Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study,” were published in The Lancet.

The international, multicenter KEYNOTE-040 trial (NCT02252042) — sponsored by Merck, known as MSD outside the U.S. and Canada — was led by a team at The Institute of Cancer Research (ICR) in London, and The Royal Marsden NHS Foundation Trust.

It included 495 patients whose head and neck SCC had spread during or after platinum-containing chemotherapy, or whose disease recurred or progressed within three to six months of previous combination therapy containing platinum.

A total of 247 patients received a Keytruda infusion every three weeks, while 248 were treated with standard doses of methotrexate, Taxotere (docetaxel), or the targeted therapy Erbitux (cetuximab, by Eli Lilly).

Results showed that 37% patients on Keytruda survived for at least one year, compared to 26.5% of those on chemotherapy with methotrexate or Taxotere, or taking Erbitux. Median overall survival was 8.4 months with Keytruda and 6.9 months with standard treatment.

Response rates were similar among the two groups of patients — 14.6% versus 10.1%, but patients who responded to the immunotherapy had responses lasting a median of 18.4 months, compared to five months with standard care. Some patients were still cancer-free three years after the first Keytruda dose.

Keytruda is a type of therapy called immune checkpoint inhibitor, which binds to the PD-1 protein on immune T-cells to block the interaction of PD-1 with its ligand, PD-L1, in cancer cells — a mechanism used by tumors to evade immune attacks.

Keytruda treatment was more beneficial in patients whose tumors expressed PD-L1, matching data in other cancer types.

“Of note, all four complete responses and 30 of 32 partial responses in the pembrolizumab group occurred in patients with a PD-L1 combined positive score of 1 or higher,” the study reported.

Treatment with Keytruda was also associated with less frequent severe (grade 3) or worse adverse events — 13% versus 36%. The most common treatment-related side effects were hypothyroidism with Keytruda (in 33 patients) and fatigue with standard of care (43 patients). Treatment-related deaths occurred in four patients receiving the immunotherapy and two on standard treatment.

“The clinically meaningful prolongation of overall survival and favourable safety profile of pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinoma support the further evaluation of pembrolizumab as a monotherapy and as part of combination therapy in earlier stages of disease,” the researchers wrote.

Early results of this Phase 3 study were presented in September 2017 at the European Society for Medical Oncology (ESMO) 2017 Congress in Madrid. The trial is set to fully conclude in January.

Kevin Harrington, a professor of biological cancer therapies at ICR, and consultant at The Royal Marsden, noted that the study population typically has poor outcomes, as treatment options for head and neck cancer that comes back or spreads are limited.

“Our findings show that the immunotherapy pembrolizumab extends the life of people with advanced head and neck cancer overall, and in a group of patients has really dramatic benefits,” Harrington said in a press release. “It is also a much kinder treatment than those currently approved.”

Harrington also expressed his desire to see Keytruda approved for these patients so that they “can be offered the chance of a longer life and improved quality of life.”

“There is also an urgent need to work out how we can identify in advance which patients are likely to benefit, given that some of these people may do much better than they do on standard treatment,” he added.

“The next big challenge,” said Paul Workman, ICR’s chief executive “is to design immunotherapies that can work for many more people, so that more patients can benefit from the kinds of dramatic responses that we saw in some patients in this trial.”

Derek Kitcherside, 69, who was profiled in the release, is alive and well after two years of treatment. “I was first diagnosed with cancer of the larynx back in 2011 but quickly went into remission after having standard treatments.” He started experiencing symptoms again, such as coughing up blood, in January 2014. “I thought it was the reoccurrence of the same cancer, but it turned out three or four tumours had spread to my right lung.” He was diagnosed with head and neck SCC, “which was inoperable and probably incurable.”

Kitcherside did not respond to radiotherapy and chemotherapy. He then joined KEYNOTE-040, starting treatment in May 2015. “I travelled down from Leicester every three weeks for two years. My tumour was shrinking all the time and I felt a bit better every time I went — it made a huge difference to my life and I was able to return to normality,” he said.

His disease remains stable, with gradual tumor shrinkage seen on regular computed tomography scans. “It’s remarkable how I’ve responded to [Keytruda] and I don’t think I’d be here without it.”

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