publication date: Apr. 20, 2018

Clinical Roundup

Keytruda combination improved OS regardless of PD-L1 expression, including patients who tested negative for PD-L1

Merck announced results from KEYNOTE-189, a pivotal phase III trial evaluating Keytruda (pembrolizumab) in combination with pemetrexed (Alimta) and cisplatin or carboplatin for the first-line treatment of metastatic nonsquamous non-small cell lung cancer.

Findings showed that the Keytruda-pemetrexed-platinum chemotherapy combination significantly improved overall survival (OS), reducing the risk of death by half compared with chemotherapy alone (HR=0.49 [95% CI, 0.38-0.64]; p<0.00001). In pre-specified exploratory analyses, an OS benefit was observed regardless of PD-L1 expression in the three PD-L1 categories that were evaluated, including: patients whose tumors were negative for PD-L1 (HR=0.59 [95% CI, 0.38-0.92]); patients whose tumors had PD-L1 tumor proportion scores (TPS) of 1-49 percent (HR=0.55 [95% CI, 0.34-0.90]); and patients who had a TPS of greater than or equal to 50 percent (HR=0.42 [95% CI, 0.26-0.68]).

The addition of Keytruda to pemetrexed plus platinum chemotherapy also achieved a significant improvement in progression-free survival (PFS), with a reduction in the risk of progression or death of nearly half for patients in the Keytruda combination arm, compared with chemotherapy alone (HR=0.52 [95% CI, 0.43-0.64]; p<0.00001). A PFS improvement in the Keytruda combination group was observed in patients whose tumors were negative for PD-L1 (HR=0.75 [95% CI, 0.53-1.05]); patients with a TPS of 1-49 percent (HR=0.55 [95% CI, 0.37-0.81]); and patients with a TPS greater than or equal to 50 percent (HR=0.36 [95% CI, 0.25-0.52]).

These results are being presented today in a plenary session at the American Association for Cancer Research Annual Meeting, with simultaneous publication in The New England Journal of Medicine.

“In this trial, Keytruda in combination with pemetrexed and platinum chemotherapy, compared with chemotherapy alone, prolonged overall survival and progression-free survival in patients with advanced nonsquamous non-small cell lung cancer regardless of PD-L1 expression,” said Leena Gandhi, director of thoracic medical oncology at NYU Langone’s Perlmutter Cancer Center and lead author of The New England Journal of Medicine paper. “There is good scientific rationale for combining Keytruda with pemetrexed and platinum chemotherapy, and these clinical data now suggest this combination as a new standard of care for the first-line treatment of these nonsquamous non-small cell lung cancer patients.”

 

Keytruda reduced risk of recurrence or death by over 40% vs. placebo as adjuvant therapy in resected, high-risk stage III melanoma

Merck and the European Organisation for Research and Treatment of Cancer announced findings from the phase III EORTC1325/KEYNOTE-054 trial investigating Keytruda (pembrolizumab) as adjuvant therapy in resected, high-risk stage III melanoma.

Study results showed Keytruda significantly prolonged recurrence-free survival (RFS), reducing the risk of disease recurrence or death by 43 percent compared to placebo in the overall study population (HR=0.57 [98.4% CI, 0.43-0.74]; p<0.0001).

For the primary endpoint of RFS in the overall study population, the one-year RFS rate was 75.4 percent (95% CI, 71.3-78.9) for Keytruda compared to 61.0 percent (95% CI, 56.5-65.1) for placebo. For the co-primary endpoint of RFS in patients whose tumors were considered PD-L1 positive, Keytruda demonstrated significantly prolonged RFS compared to placebo (HR=0.54; 95% CI, 0.42-0.69; p<0.0001). The safety profile of Keytruda was consistent with what has been seen in previous trials among patients with advanced melanoma.

These results are being presented today for the first time in the opening plenary session at the American Association for Cancer Research (AACR) Annual Meeting 2018 (Abstract #10526), with simultaneous publication in The New England Journal of Medicine.

“The EORTC is very pleased to have collaborated with Merck on this important study which showed a significant recurrence-free survival benefit across all stage III melanoma,” said Alexander Eggermont, study chair, director general at the Gustave Roussy Cancer Institute, professor of oncology, University of Paris-Saclay.

 

SU2C researchers find treatment strategy for stage I-III NSCLC 

An immunotherapy administered prior to surgery is yielding outcomes in 45% of patients treated in this small study from researchers on the Stand Up to Cancer-Cancer Research Institute Cancer Immunology Dream Team, who is a scientific partner of Stand Up to Cancer, according to results presented at the American Association for Cancer Research Annual Meeting. It was published online in The New England Journal of Medicine.

Scientists at Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy and Memorial Sloan Kettering Cancer Center found that administering two doses of the Bristol-Myers Squibb anti-PD1 immunotherapy Opdivo (nivolumab) for several weeks prior to surgery was not only safe but 45 percent of the patients in the trial responded so well that there was little evidence of the cancer remaining upon follow-up. In addition, the patients’ immune systems also likely destroyed straggler tumor cells still circulating in the blood system, which can later take hold and lead to recurrence and metastasis.

This Dream Team’s approach, designed to arrest disease progression within the microenvironment, expands the scope of SU2C’s Cancer Interception research portfolio. SU2C is currently funding four Cancer Interception teams focusing on lung and pancreatic cancer.

In addition to the named Interception Teams, three additional SU2C-funded teams are engaged in interception-like approaches to treat multiple myeloma, colon cancer and ovarian cancer.

Historically, chemotherapy or chemoradiotherapy, is given to lung cancer patients to shrink a large, non-metastasized tumor, and in the past, immunotherapeutic agents have been administered after surgery with limited results.

SU2C-CRI Dream Team researchers hypothesized that leaving the tumor in place during initial treatment with immunotherapy would turn it into an “auto-vaccine” resulting in the activation of tumor-specific T cells that would then circulate through the body and find distant sites of micrometastases, thereby preventing relapse post-surgery which can happen to at least one-half of lung cancer patients who undergo surgery.

After a median follow-up of 12 months, three-quarters of the patients who underwent surgical resection were alive and recurrence-free. Recurrence-free survival at 18 months was 73 percent, and the median recurrence-free survival had not been reached at the time of data analysis. To date, only one patient has died of cancer recurrence after surgery. SU2C is cautious not to compare these outcomes with historical outcomes given that it was a small study.

Copyright (c) 2018 The Cancer Letter Inc.