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SAN ANTONIO -- A maintenance strategy involving checkpoint blockade and a PARP inhibitor after first-line therapy did not improve survival outcomes in unselected patients with triple-negative breast cancer (TNBC), though was associated with a good safety profile, a phase II trial indicated.

Patients in the open-label KEYLYNK-009 study had responding or stable disease following induction treatment with pembrolizumab (Keytruda) and platinum-based chemotherapy for locally recurrent inoperable or metastatic TNBC.

With a median follow-up of 17 months, progression-free and overall survival (PFS, OS) were essentially identical whether patients went on to receive maintenance pembrolizumab plus olaparib (Lynparza) or continued with pembrolizumab plus chemotherapy:

• PFS: 5.5 vs 5.6 months, respectively (HR 0.98, 95% CI 0.72-1.33)
• OS: 25.1 vs 23.4 months (HR 0.95, 95% CI 0.64-1.40)

"It is important to keep in mind ... that these patients have already received a median of 4.2 months of induction chemotherapy, and that is not included in the PFS and OS numbers," said Hope Rugo, MD, of the University of California San Francisco Helen Diller Family Comprehensive Cancer Center, who presented the findings at the annual San Antonio Breast Cancer Symposium.

A trend toward a more favorable PFS was observed with the chemotherapy-free strategy in the subgroup with a BRCA mutation (12.4 vs 8.4 months; HR 0.70, 95% CI 0.33-1.48).

"Perhaps maintenance with pembrolizumab plus olaparib could be an effective strategy for patients with germline BRCA mutations receiving immunotherapy with induction chemotherapy," said Rugo, but noted the finding requires confirmation in larger trials.

Eligible patients for had locally recurrent inoperable or metastatic TNBC not previously treated in the metastatic setting. All patients had responded to or had stable disease following induction chemotherapy with four to six cycles of weekly carboplatin-gemcitabine plus pembrolizumab (200 mg every 3 weeks).

Of the 460 participants who began induction, 271 were randomized to maintenance with pembrolizumab plus either olaparib (300 mg twice-daily) or carboplatin-gemcitabine at the same dosages used for induction (189 patients were not randomized because of disease progression).

At baseline, 48% of the randomized patients had a PD-L1 combined positive score (CPS) of ≥10 and 22% had a BRCA mutation. About two-thirds had recurrent metastatic disease, and 70% had a complete or partial response to induction therapy.

Landmark analyses at 12 months showed PFS rates of 33% in the pembrolizumab-olaparib arm and 29% in the pembrolizumab-chemotherapy arm. OS rates at 18 months were 62% and 56%, respectively.

As in the overall study population, OS rates among patients with a CPS ≥10 were not different between treatment arms (HR 0.97, 95% CI 0.53-1.76).

As expected, investigators observed fewer treatment-related adverse events (TRAEs) in patients receiving pembrolizumab and olaparib versus pembrolizumab and chemotherapy, including markedly fewer grade ≥3 TRAEs (33% vs 68%, respectively). Treatment discontinuation for TRAEs occurred in 9% of patients in the olaparib arm and 20% of the chemotherapy arm. Rates of immune-mediated adverse events were similarly low in each arm.

Rugo said the lower incidence of TRAEs in patients receiving pembrolizumab and olaparib was clinically significant. Furthermore, she said, data suggest that "in patients receiving chemo and pembrolizumab who have a great response or stable disease, you can drop the chemo and continue pembrolizumab without it impacting outcomes."

The KEYLYNK-009 data are reassuring in that clinicians can safely choose between a PARP inhibitor or continuing chemotherapy as add-ons to pembrolizumab as maintenance, with the knowledge that the side effect profile is slightly better with olaparib, Allison Kurian, MD, MSc, of Stanford University in Palo Alto, California, told 澳门老奇人论坛.

The trial selected for patients who are platinum-sensitive in the induction setting, and these same patients are also likely to respond to a PARP inhibitor, "so on some level it's not too surprising to me that you could use either a platinum agent or a PARP inhibitor after successful induction with chemotherapy," she said.

Kurian added that future studies should explore the possibility of using pembrolizumab alone for maintenance after response to induction therapy with pembrolizumab and chemotherapy. Dropping chemotherapy in the maintenance setting in favor of pembrolizumab alone "while not a standard of care, is what we do in the clinic," she said.

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