Pembrolizumab demonstrates survival benefit in some lung cancer patients

CHICAGO — First-line pembrolizumab conferred longer median OS than chemotherapy among patients with non-small cell lung cancer and PD-L1 expression, according to results of the phase 3 KEYNOTE-042 clinical trial presented during the plenary session at ASCO Annual Meeting.

Patients with a PD-L1 expression of 1% or greater first treated with pembrolizumab (Keytruda, Merck) lived a median of 4 to 8 months longer than patients who received chemotherapy.

Gilberto Lopes, MD, MBA, medical director of international programs at Sylvester Comprehensive Cancer Center of University of Miami Health System, and colleagues randomly assigned 1,274 patients with locally advanced or metastatic NSCLC without EGFR mutations or ALK translocation to receive 200 mg pembrolizumab every 3 weeks (n = 637) or investigator’s choice of maximum six cycles of paclitaxel plus carboplatin or pemetrexed plus carboplatin (n = 637) with optional pemetrexed maintenance for nonsquamous disease.

Among the patients, 599 had tumor PD-L1 expression score of at least 50%, 818 had at least 20% PD-L1 expression, and every patient had at least 1% PD-L1 expression.

Pembrolizumab significantly improved OS among patients with a tumor proportion score of more than 50% (median OS, 20 months vs. 12.2 months; HR = 0.69; 95% CI, 0.56-0.85), more than 20% (17.7 months vs. 12 months; HR = 0.77; 95% CI, 0.64-0.92) and more than 1% (16.7 months vs. 12.1 months; HR = 0.81; 95% CI, 0.71-0.93).

Additionally, previous results from the KEYNOTE-024 trial showed pembrolizumab was superior to chemotherapy as first-line therapy for patients with advanced NSCLC with a PD-L1 tumor progression score of at least 50% and no sensitizing EGFR mutations and ALK translocations.

The data presented in KEYNOTE-042 included results from a patient population that was already shown to benefit from pembrolizumab, according to Timothy F. Burns, MD, PhD, a medical oncologist at UPMC Hillman Cancer Center.

“If we analyzed the data, patients within the greater than 1% and greater than 20% PD-L1 expression subset all met their primary endpoint,” Burns told HemOnc Today.

However, as Burns said, there was almost no benefit in the subset of patients between 20% and 50% PD-L1 expression were analyzed.

“All the benefit essentially came from the [patients within] the greater than 50% subset,” Burns said. “In that greater than 1% subset, there was a benefit, but it seemed to come from all of those subsets of patients that were over 50%.”

“So, did it change practice?” Burns said. “No, it didn’t.”

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For instance, if a patient presents with a PD-L1 tumor progression score of less than 50% they will likely get chemotherapy plus pembrolizumab, he said.

Additionally, if a patient presents with a score greater than 50%, treatment choice will still likely revolve around patient factors.

“If a patient has large tumors that need response, they’ll probably receive [each therapy],” he said, “But, if the patient is frail they will probably get monotherapy alone.”

In conversations with some community physicians after the presentation, Burns said there was a belief that every patient was now able to receive pembrolizumab.

“Although there’s this message that this may likely receive approval for patients with a PD-L1 expression greater than 1%, a patient is likely not really benefiting if they don’t present with a greater than 50% PD-L1 expression,” he said. “In fact, this may have created some confusion.” – by Ryan McDonald

Reference:

Lopes G, et al. Abstract LBA4. Presented at: ASCO Annual Meeting; June 1-5,2018; Chicago.

Disclosures: Burns reports no relevant financial disclosures.