The FDA has approved pembrolizumab plus paclitaxel with/without bevacizumab for PD-L1–positive platinum-resistant ovarian cancer.
The FDA has approved pembrolizumab (Keytruda) as well as pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) in combination with paclitaxel, with or without bevacizumab (Avastin), for the treatment of adult patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with a PD-L1 combined positive score (CPS) of at least 1, as determined by an FDA-authorized test, and prior receipt of 1 or 2 systemic treatment regimens.1
In conjunction with this indication, the FDA also approved the PD-L1 IHC 22C3 pharmDx assay as a companion diagnostic to identify patients with PD-L1–positive epithelial ovarian, fallopian tube, or primary peritoneal carcinoma eligible for pembrolizumab-based therapy.
The approval is supported by efficacy and safety findings from the phase 3 KEYNOTE-B96 trial (NCT05116189), which evaluated pembrolizumab in combination with paclitaxel, with or without bevacizumab, in patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma who had received 1 or 2 prior lines of systemic therapy.
Findings from the study showed that among patients whose tumors expressed PD-L1 with a CPS of at least 1 (n = 466), treatment with pembrolizumab plus paclitaxel with or without bevacizumab resulted in a median progression-free survival (PFS) of 8.3 months (95% CI, 7.0-9.4) compared with 7.2 months (95% CI, 6.2-8.1) with placebo plus paclitaxel with or without bevacizumab (HR, 0.72; 95% CI, 0.58-0.89; P = .0014).
Furthermore, in this PD-L1–positive population, the median overall survival (OS) was 18.2 months (95% CI, 15.3-21.0) in the pembrolizumab arm vs 14.0 months (95% CI, 12.5-16.1) in the placebo arm (HR, 0.76; 95% CI, 0.61-0.94; P = .0053).
KEYNOTE-B96 is a multicenter, randomized, double-blind, placebo-controlled phase 3 trial that enrolled 643 patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma who had received 1 or 2 prior lines of systemic therapy.1,2 Eligible patients were required to have received at least 1 prior platinum-based chemotherapy regimen and to have demonstrated radiographic disease progression within 6 months of the last platinum dose. Investigators randomly assigned patients 1:1 to receive pembrolizumab plus paclitaxel with or without bevacizumab or placebo plus paclitaxel with or without bevacizumab.
The study’s primary objective was to compare pembrolizumab plus paclitaxel with or without bevacizumab with placebo plus paclitaxel with or without bevacizumab with respect to PFS per RECIST 1.1 criteria per investigator assessment.1
The overall safety profile of pembrolizumab in combination with paclitaxel, with or without bevacizumab, was consistent with that observed in prior clinical trials across cancer types.1 The prescribing information for pembrolizumab includes warnings and precautions about immune-mediated adverse effects, infusion-related reactions, complications associated with allogeneic hematopoietic stem cell transplantation (HSCT), and embryo-fetal toxicity.
Of note, the recommended dose of pembrolizumab is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression or unacceptable toxicity, or for up to 24 months. The recommended dose of pembrolizumab and berahyaluronidase alfa-pmph is 395 mg/4800 units every 3 weeks or 790 mg/9600 units every 6 weeks until disease progression or unacceptable toxicity, or for up to 24 months.
Safety considerations for pembrolizumab include the risk of immune-mediated adverse reactions, which may be severe or fatal and can occur in any organ system or tissue, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, and solid organ transplant rejection. Clinicians should monitor for early identification and management, including evaluation of liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment, and withhold or permanently discontinue pembrolizumab based on the type and severity of the reaction.
According to the updated prescription label, additional warnings and precautions include infusion-related reactions, for which infusion interruption, rate reduction, or permanent discontinuation may be required depending on severity; complications of allogeneic HSCT, including fatal effects, in patients receiving HSCT before or after PD-1/PD-L1 blockade; and a recommendation that treatment of multiple myeloma with a PD-1/PD-L1 inhibitor in combination with a thalidomide analogue plus dexamethasone is not recommended outside controlled clinical trials.3 Pembrolizumab also carries a warning for embryo-fetal toxicity and may cause fetal harm; females of reproductive potential should be advised of the potential risk to a fetus.
Across pembrolizumab-containing regimens, commonly reported adverse reactions include nausea, neutropenia, diarrhea, hypertension, thrombocytopenia, constipation, arthralgia, vomiting, urinary tract infection, rash, leukopenia, hypothyroidism, decreased appetite, pyrexia, epistaxis, decreased white blood cell count, and stomatitis. Additional regimen-specific adverse reactions have been observed in combination settings, including with axitinib (eg, diarrhea, fatigue/asthenia, hypertension, hepatotoxicity, hypothyroidism, palmar-plantar erythrodysesthesia, stomatitis/mucosal inflammation) and with lenvatinib (eg, hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, proteinuria, hemorrhagic events, hepatotoxicity, acute kidney injury), as well as with enfortumab vedotin (eg, rash, peripheral neuropathy, fatigue, pruritus, diarrhea, alopecia, dry eye).
