FDA Approves Keytruda Combination for Non-Small Cell Lung Cancer Subset

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The immunotherapy agent received approval for the treatment of metastatic squamous non-small cell lung cancer.

The Food and Drug Administration (FDA) approved the combination use of Keytruda (pembrolizumab) plus carboplatin and either paclitaxel or nab-paclitacel to treat patients with metastatic squamous non-small cell lung cancer (NSCLC) – a disease that accounts for 20 to 30 percent of all lung cancers – according to Merck, the manufacturer of the immunotherapy agent.

The agency based its approval on results from the phase 3 KEYNOTE-407 trial, which was recently presented at the International Association for the Study of Lung Cancer 19th World Conference on Lung Cancer. The trial randomized 559 patients to receive either 200 mg of Keytruda (278 patients) or placebo (281 patients) on the first day of 35 cycles. For the first four cycles, all the patients also received carboplatin and either paclitaxel or nanoparticle albumin-bound [nab]–paclitaxel. Patients were followed for a median of 7.8 months.

The Keytruda regimen prolonged median overall survival by 4.6 months (15.9 months vs. 11.3 months) and median progression-free survival by 1.6 months (6.4 months vs. 4.8 months). Keytruda’s survival benefit was consistent, regardless of PD-L1 expression among patients treated with the agent.

In addition, the Keytruda regimen demonstrated superior response rates (57.9 percent vs. 38.4 percent) compared with placebo, reducing the risk of disease progression or death by 44 percent.

Grade 3 or higher side effects occurred in 69.8 percent of patients treated with Keytruda, including neutropenia (22.7 percent), anemia (15.5 percent), thrombocytopenia (6.8 percent) and diahrrea (4 percent).

This is Keytruda’s fifth approval in the lung cancer space. The drug is also approved to treat certain types of melanoma, head and neck cancer, classical Hodgkin lymphoma, urothelial carcinoma, microsatellite instability-high (MSI-H) solid tumors, gastric cancer and cervical cancer.

“Today’s approval expands our current lung cancer indications to include combination treatment in patients with squamous cell carcinoma, a type of lung cancer that is particularly difficult to treat,” said Roger M. Perlmutter, M.D., Ph.D., president, Merck Research Laboratories. “Approval by the FDA has the potential to mean that KEYTRUDA can be used to improve survival for more patients with this debilitating disease.”

Maintenance Lynparza Improves PFS for Ovarian Cancer

The PARP inhibitor Lynparza (olaparib) significantly improved progression-free survival (PFS) as frontline maintenance therapy for women with BRCA-positive advanced ovarian cancer, according to findings from the randomized phase 3 SOLO-1 trial presented at the 2018 ESMO Congress.

The PARP inhibitor Lynparza (olaparib) significantly improved progression-free survival (PFS) as frontline maintenance therapy for women with BRCA-positive advanced ovarian cancer, according to findings from the randomized phase 3 SOLO-1 trial presented at the 2018 ESMO Congress.

With a median follow-up of 41 months, the median PFS by independent central review was not reached in the Lynparza arm (260 patients), versus 14.1 months in the placebo arm (131 patients). The investigator-assessed PFS in the Lynparza arm was not reached, compared to 13.8 months in the placebo arm. Although the median PFS for Lynparza has not yet been reached, Moore said that it looks to be an approximate three-year advantage over placebo.

"We feel that the SOLO-1 trial has demonstrated an unprecedented improvement in the progression-free survival in patients with a BRCA mutation who have advanced ovarian cancer when olaparib is incorporated following platinum-based chemotherapy,” said Kathleen Moore, M.D., associate professor, Stephenson Cancer Center, University of Oklahoma, and principal investigator of SOLO-1, during a press conference at the meeting.

The ongoing SOLO-1 trial (NCT01844986) is evaluating maintenance Lynparza following platinum-based chemotherapy in newly-diagnosed patients with advanced ovarian cancer with a BRCA1/2 mutation. Patients with newly diagnosed, FIGO stage 3-4, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer with germline or somatic BRCA mutations were enrolled. These patients must have also received cytoreductive surgery, and be in clinical complete response or partial response after platinum-based chemotherapy.

The study treatment in SOLO-1 continued until disease progression, and treatment was ceased for patients with no evidence of disease at two years. Although, patients with a partial response at two years could continue treatment.

Secondary endpoints of the trial were PFS2, which is defined as time from randomization to second progression event, overall survival, and quality of life.

Patients who received Lynparza maintenance showed a statically significant improvement in PFS2, with a median PFS2 not reached, compared with 41.9 months in the placebo group. Overall survival data are not yet mature, noted Moore. Regarding quality of life, there were no clinically relevant changes. The discontinuation rate in the Lynparza arm was 12 percent.

“It is estimated that over 50 percent of women on the olaparib arm were still progression free at four years as compared to only 11 percent for placebo,” said Moore. “A key point here is that there was no change in the Kaplan-Meier curve at the 2-year mark when we stopped the olaparib or placebo therapy. So, it appears that the benefit of olaparib maintenance is extended beyond even the 2-year timepoint in which patients were receiving treatment.”

Adverse events (AEs) observed were low-grade, with the most common grade 3 or higher AEs in the Lynparza arm being anemia (22 percent) and neutropenia (8 percent). Baseline characteristics, including health-related quality-of-life scores, were balanced between the two arms.

“While ovarian cancer is a highly treatable disease due in large part to its exquisite chemosensitivity, the percentage of patients who survive disease-free for long periods of time is dismally low, and hovers in the 10 percent to 15 percent range,” Moore noted. “If we are going to make meaningful improvements on that rate, it has to be with improvements in frontline treatment.”

The majority of patients with ovarian cancer recur within three years of diagnosis, Moore said. Although their disease has the potential to be treated, those patients are no longer considered treatable. Moore emphasized the importance of SOLO-1, as it is the first phase 3 large prospective data set for this population of women.

“Maintenance olaparib should be considered standard treatment following platinum-based chemotherapy for women with newly diagnosed advanced ovarian cancer and a BRCA mutation,” concluded Moore.

Additionally, panelists at the press conference suggested that the field should be looking to the possibility of extrapolating this data to other high-grade serous carcinomas.

Lynparza is not currently approved by the FDA as a first-line maintenance treatment for newly diagnosed patients with BRCA-positive ovarian cancer. The PARP inhibitor is FDA approved for the maintenance treatment of recurrent ovarian cancer in response to platinum-based chemotherapy regardless of BRCA mutation status, and for the treatment of advanced ovarian cancer patients with a germline BRCA mutation previously treated with three or more lines of chemotherapy.

A version of this article originally appeared on onclive.com with the title, "Olaparib Substantially Improves PFS as Frontline Maintenance in Ovarian Cancer."

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