Addition of pembrolizumab to chemotherapy improves outcomes in advanced NSCLC

MADRID — The addition of pembrolizumab to pemetrexed and carboplatin for first-line therapy extended survival and improved response rates among previously untreated patients with advanced nonsquamous non-small cell lung cancer, according to study results presented at the European Society for Medical Oncology Congress.

“The hazard ratio for overall survival continues to improve for pembrolizumab plus pemetrexed and carboplatin versus pemetrexed and carboplatin alone,” Hossein Borghaei, DO, MS, chief of thoracic medical oncology and director of lung cancer risk assessment at Fox Chase Cancer Center, said during his presentation.

The open-label, randomized phase 2 KEYNOTE-021 study included 123 patients with stage IIIB/stage IV nonsquamous NSCLC who had received no prior systemic therapy and had no EGFR mutation or ALK translocation.

Researchers randomly assigned patients 1:1 to four cycles of carboplatin area under the curve 5 plus pemetrexed 500 mg/m² every 3 weeks with or without the anti-PD-1 therapy pembrolizumab (Keytruda, Merck) 200 mg every 3 weeks.

Sixty patients (median age, 62.5 years) received the pembrolizumab regimen and 63 patients (median age, 66 years) received chemotherapy alone.

Patients assigned the pembrolizumab regimen who experienced radiologic progression could cross over to pembrolizumab monotherapy.

Initial analysis of the open-label, randomized phase 2 KEYNOTE-021 study, performed after median follow-up of 10.6 months, the combination of pemetrexed, carboplatin and pembrolizumab conferred a significant improvement in objective response rate (55% vs. 29%; P = .0016) and PFS (HR = 0.53; P = .01) compared with pemetrexed and carboplatin alone. At that time, the improvement in OS (HR = 0.9) for the pembrolizumab regimen was not statistically significant.

As reported at this year’s ASCO Annual Meeting, improvements in ORR and PFS persisted at median follow-up of 14.5 months. By that time, the HR for OS had improved to 0.69 but still was not statistically significant.

At ESMO, Borghaei presented updated efficacy and safety data for the combination based on follow-up of 18.7 months.

By that point, patients assigned the triplet therapy had achieved a significantly higher ORR (56.7% vs. 31.7%; P = 0.0029). A significantly higher percentage of patients assigned that regimen also remained progression free (52% vs. 29%; P = 0.0067).

The 18-month OS rate was 70% with pembrolizumab and 56% for chemotherapy alone. The HR for OS at this time further improved to 0.59 (95% CI, 0.34-1.05).

“The incremental [improvement in] overall survival, although not statistically significant, continues, and the combination continues to have a favorable and manageable toxicity profile,” Borghaei said. “That’s why I’ve decided to utilize the data in everyday practice.”

At the most recent analysis point, incidence of grade 3 to grade 5 toxicities was higher among patients assigned the pembrolizumab regimen (41% vs. 18%).

Future studies will determine whether the triple therapy would be appropriate for patients with greater than 50% PD-L1 expression, Borghaei said.

“If I have someone with really high disease burden — and you see this from time to time in lung cancer patients — and I really want to have an improvement in my response rate above and beyond chemotherapy, I do offer the combination if somebody has a lower level of expression,” Borghaei said. “A 55% response rate can be meaningful for someone who has a huge tumor burden.” – by Chuck Gormley

Reference:

Borghaei H, et al. Abstract LBA49. Presented at: European Society for Medical Oncology Congress; Sept. 8-12, 2017; Madrid.

Disclosures: Merck funded this study. Borghaei reports advisory roles with Bristol-Myers Squibb, Eli Lilly, Celgene, Genentech, Novartis, AstraZeneca, Trovagene, EMD Serono, Pfizer and Merck; research funding from Celgene, Millennium and Merck; and honoraria from Celgene. Please see the abstract for a list of all other researchers’ relevant financial disclosures.