Patients had improved response rates with pembrolizumab every 2 weeks (33.7%) and every 3 weeks (32.9%) compared with ipilimumab (11.9%; P < .001 for both comparisons).

After a median follow-up of 7.9 months, ongoing responses occurred in 89.4% of pembrolizumab every 2 weeks, 96.7% of pembrolizumab every 3 weeks, and 87.9% of patients who received ipilimumab.

Both pembrolizumab arms had lower rates of grade 3 to 5 adverse events (13.3% at 2 weeks, 10.1% at 3 weeks) than the ipilimumab arm (19.9%).


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“We would like to have a better understanding of when pembrolizumab alone is adequate and when we need to add another agent such as epacadostat or ipilimumab in combination to get a response,” explained Adil Daud, MD, senior author of Keynote-002 and co-author of Keynote-006, and a professor in the department of medicine (hematology/oncology) at the University of California, San Francisco.

Management of immune-related adverse events continues to be a major challenge in treatment with pembrolizumab. The most common adverse events related to immunotherapy include rash, colitis, hepatitis, pneumonitis, and endocrinopathies.

“Careful follow-up of patients, early discontinuation, and use of immune suppressing steroids are the best methods. Future tests may be able to determine if someone has autoimmune antibodies or autoimmune T cells, the numbers of which we may be able to decrease,” said Dr Daud.

Prospectively validated biomarkers are lacking. Baseline characteristics such as lactate dehydrogenase (LDH) and lymphocyte count can serve as strong predictors of PFS and OS. Additional factors, such as gender and previous treatment with ipilimumab, can predict response to treatment with pembrolizumab.

While expression of PD-L1 on tumor cells predicts durability of response to pembrolizumab, absence of PD-L1 does not necessarily indicate a patient will not have a durable response.

Some approaches could improve this need for prospectively validated biomarkers.

“We need a marker that has a wide dynamic range and adds to the various clinical factors that are currently available such as location of metastases, size of metastases, and LDH,” said Dr Daud.

Patient enrollment on clinical trials may hasten these discoveries. Clinicians are encouraged to recommend relevant clinical trials to their patients.

References

  1. Tsao H, Atkins MB, Sober AJ. Management of cutaneous melanoma. N Engl J Med. 2004;351(10):998-1012.
  2. Specenier P. Pembrolizumab use for the treatment of advanced melanoma. Expert Opin Biol Ther. 2017 Apr 3. doi: 10.1080/14712598.2017.1309388 [Epub ahead of print]
  3. Ribas A, Puzanov I, Dummer R, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015;16(8):908-18.
  4. Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521-32.