Nivolumab-ipilimumab combination benefits women with advanced cervical cancer

Wendel R Naumann, MD
R. Wendel Naumann

BARCELONA, Spain — Nivolumab in combination with ipilimumab conferred clinical benefit for women with recurrent or metastatic cervical cancer regardless of PD-L1 status, according to results of the randomized phase 1b/phase 2 CheckMate 358 study presented at European Society for Medical Oncology Congress.

“This is the most exciting data we have ever seen [among women] with metastatic cervical cancer,” R. Wendel Naumann, MD, professor and associate director of gynecologic oncology at Levine Cancer Institute at Atrium Health, told HemOnc Today. “Responses were similar [among women with PD-L1-positive and PD-L1-negative disease], which suggests that this type of treatment would benefit all women with squamous cell cancer of the cervix.”

The current standard of care for recurrent or metastatic disease without prior systemic therapy is cisplatin/paclitaxel in combination with bevacizumab [Avastin, Genentech]. Subsequent treatment options are limited.

“Upregulation of PD-1 and PD-L1 expression has been reported in cervical cancer, making this tumor type likely to respond to PD-1/PD-L1-based therapy. CTLA-4 is another inhibitory checkpoint playing a key role in regulating adaptive immunity,” researcher Ana Oaknin, MD, PhD, head of the gynecological tumor unit and clinical investigator with the gynecologic cancer research program at Vall d’Hebrὁn Institute of Oncology in Spain, said during a presentation at ESMO.

Results from a separate arm of the CheckMate 358 study released earlier this year showed nivolumab (Opdivo, Bristol-Myers Squibb) demonstrated efficacy for women with recurrent or metastatic cervical, vaginal or vulvar cancers.

The portion of the study presented at ESMO included 91 women.

Researchers randomly assigned 45 women to nivolumab dosed at 3 mg/kg twice weekly plus ipilimumab (Yervoy, Bristol-Myers Squibb) dosed at 1 mg/kg six times a week (combination A). The other 46 women received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg three times per week, followed by nivolumab dosed at 240 mg twice weekly (combination B).

Treatment continued for up to 24 months, or until disease progression or unacceptable toxicity.

Investigator-assessed objective response rate served as the study’s primary endpoint. OS, PFS, and duration of response served as secondary endpoints.

Median follow-up was 10.7 months women assigned combination A and 13.9 months for women assigned combination B.

Results showed higher ORR with combination B among women who had not undergone prior systemic therapy (46% vs 32%) and those who had received prior systemic therapy (36% vs. 23%).

Median PFS with combination A was 13.8 months (95% CI, 2.1 to not reached) for women who had not received prior systemic therapy and 3.6 months (95% CI, 1.9-5.1) for women who received prior systemic therapy. Median PFS with combination B was 8.5 months (95% CI, 3.7 to not reached) for women who had not undergone prior systemic therapy and 5.8 months (95% CI, 3.5-17.2) for those who had.

Median OS among women assigned combination A was not reached (95% CI, 17.4 to not reached) for women without prior systemic therapy and 10.3 months (95% CI, 7.9-15.2) for women who underwent prior systemic therapy. Median OS among women assigned combination B was not reached for women who had not undergone prior systemic therapy (95% CI, 13.9 to not reached) and 25.4 months for women who had undergone prior systemic therapy (95% CI, 17.5 to not reached).

Researchers reported comparable rates of grade 3 (80% vs. 82.6%) and grade 4 (28.9% vs. 37%) adverse events among women assigned combination A and combination B.

“The results suggest clinical benefit with both regimens of nivolumab in combination with ipilimumab [for] patients with recurrent/metastatic cervical cancer,” Oaknin said. “Given the limited treatment options for [these patients], these data are of strong clinical interest and warrant further investigation in this patient population.”– by John DeRosier

Reference:

Naumann W, et al. Abstract LBA62. Presented at: European Society for Medical Oncology; Sept. 27-Oct. 1, 2019; Barcelona, Spain.

Disclosures: Bristol-Myers Squibb funded this study. Naumann reports research/grant funding to his institution from, consultant/advisory roles with or speakers bureau roles with or expert testimony for AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Genentech, Janssen, Merck, OncoMed, Sutro Biopharma and Tesaro. Oaknin reports consultant roles with, speakers’ bureau roles with, and travel expenses from AstraZeneca, Clovis Oncology, Immunogen, PharmaMar, Roche and Tesaro, as well as research funding to her institution from Clovis Oncology, Immunogen, PharmaMar, Roche and Tesaro. Please see the abstract for all other authors’ relevant financial disclosures.

Wendel R Naumann, MD
R. Wendel Naumann

BARCELONA, Spain — Nivolumab in combination with ipilimumab conferred clinical benefit for women with recurrent or metastatic cervical cancer regardless of PD-L1 status, according to results of the randomized phase 1b/phase 2 CheckMate 358 study presented at European Society for Medical Oncology Congress.

“This is the most exciting data we have ever seen [among women] with metastatic cervical cancer,” R. Wendel Naumann, MD, professor and associate director of gynecologic oncology at Levine Cancer Institute at Atrium Health, told HemOnc Today. “Responses were similar [among women with PD-L1-positive and PD-L1-negative disease], which suggests that this type of treatment would benefit all women with squamous cell cancer of the cervix.”

The current standard of care for recurrent or metastatic disease without prior systemic therapy is cisplatin/paclitaxel in combination with bevacizumab [Avastin, Genentech]. Subsequent treatment options are limited.

“Upregulation of PD-1 and PD-L1 expression has been reported in cervical cancer, making this tumor type likely to respond to PD-1/PD-L1-based therapy. CTLA-4 is another inhibitory checkpoint playing a key role in regulating adaptive immunity,” researcher Ana Oaknin, MD, PhD, head of the gynecological tumor unit and clinical investigator with the gynecologic cancer research program at Vall d’Hebrὁn Institute of Oncology in Spain, said during a presentation at ESMO.

Results from a separate arm of the CheckMate 358 study released earlier this year showed nivolumab (Opdivo, Bristol-Myers Squibb) demonstrated efficacy for women with recurrent or metastatic cervical, vaginal or vulvar cancers.

The portion of the study presented at ESMO included 91 women.

Researchers randomly assigned 45 women to nivolumab dosed at 3 mg/kg twice weekly plus ipilimumab (Yervoy, Bristol-Myers Squibb) dosed at 1 mg/kg six times a week (combination A). The other 46 women received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg three times per week, followed by nivolumab dosed at 240 mg twice weekly (combination B).

Treatment continued for up to 24 months, or until disease progression or unacceptable toxicity.

Investigator-assessed objective response rate served as the study’s primary endpoint. OS, PFS, and duration of response served as secondary endpoints.

Median follow-up was 10.7 months women assigned combination A and 13.9 months for women assigned combination B.

Results showed higher ORR with combination B among women who had not undergone prior systemic therapy (46% vs 32%) and those who had received prior systemic therapy (36% vs. 23%).

Median PFS with combination A was 13.8 months (95% CI, 2.1 to not reached) for women who had not received prior systemic therapy and 3.6 months (95% CI, 1.9-5.1) for women who received prior systemic therapy. Median PFS with combination B was 8.5 months (95% CI, 3.7 to not reached) for women who had not undergone prior systemic therapy and 5.8 months (95% CI, 3.5-17.2) for those who had.

Median OS among women assigned combination A was not reached (95% CI, 17.4 to not reached) for women without prior systemic therapy and 10.3 months (95% CI, 7.9-15.2) for women who underwent prior systemic therapy. Median OS among women assigned combination B was not reached for women who had not undergone prior systemic therapy (95% CI, 13.9 to not reached) and 25.4 months for women who had undergone prior systemic therapy (95% CI, 17.5 to not reached).

Researchers reported comparable rates of grade 3 (80% vs. 82.6%) and grade 4 (28.9% vs. 37%) adverse events among women assigned combination A and combination B.

“The results suggest clinical benefit with both regimens of nivolumab in combination with ipilimumab [for] patients with recurrent/metastatic cervical cancer,” Oaknin said. “Given the limited treatment options for [these patients], these data are of strong clinical interest and warrant further investigation in this patient population.”– by John DeRosier

Reference:

Naumann W, et al. Abstract LBA62. Presented at: European Society for Medical Oncology; Sept. 27-Oct. 1, 2019; Barcelona, Spain.

Disclosures: Bristol-Myers Squibb funded this study. Naumann reports research/grant funding to his institution from, consultant/advisory roles with or speakers bureau roles with or expert testimony for AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Genentech, Janssen, Merck, OncoMed, Sutro Biopharma and Tesaro. Oaknin reports consultant roles with, speakers’ bureau roles with, and travel expenses from AstraZeneca, Clovis Oncology, Immunogen, PharmaMar, Roche and Tesaro, as well as research funding to her institution from Clovis Oncology, Immunogen, PharmaMar, Roche and Tesaro. Please see the abstract for all other authors’ relevant financial disclosures.

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