Study data presented Tuesday at the American Association for Cancer Research (AACR) annual meeting showed that Bristol-Myers Squibb's Opdivo (nivolumab) conferred a survival benefit in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) after platinum therapy, compared with three standard of care options. In January, the Phase III trial was halted early after an analysis by an independent Data Monitoring Committee concluded the study had met its primary endpoint of overall survival (OS). Lead investigator Maura Gillison noted that the PD-1 inhibitor was associated with improved survival "regardless of PD-L1 expression levels and HPV (human papillomavirus) status."
The CheckMate-141 study involved 361 patients with recurrent or metastatic SCCHN who had tumour progression within six months of platinum therapy in the adjuvant, primary, recurrent or metastatic setting. Patients were randomised to receive either Opdivo or monotherapy with investigator's choice of methotrexate, docetaxel or cetuximab. In addition to the primary endpoint of OS, secondary endpoints included objective response rate, progression-free survival and safety.
Results demonstrated that the Opdivo group experienced a significant 30-percent reduction in the risk of death, with a median OS of 7.5 months, versus 5.1 months for investigator's choice of therapy. In addition, Opdivo was associated with a one-year OS rate of 36 percent, compared with 16.6 percent for the control arm. Meanwhile, Bristol-Myers Squibb noted that median OS was 9.1 months in HPV-positive patients treated with Opdivo, compared to 4.4 months for the control arm, whereas among those who tested negative for HPV, Opdivo was associated with a median OS of 7.5 months, versus 5.8 months for investigator's choice of therapy.
The drugmaker also indicated that PD-L1 expression was available for 72 percent of enrolled patients and was balanced across the study arms. Results showed that Opdivo-treated participants whose tumours expressed PD-L1 in at least 1 percent of cells achieved a median OS of 8.7 months, compared with 4.6 months for the control arm, while among those with PD-L1 expression of less than 1 percent, median OS was 5.7 months in the Opdivo arm and 5.8 months for controls. Bristol-Myers Squibb noted that the safety profile of Opdivo in CheckMate-141 was consistent with prior studies, with no new safety signals identified.
Study author Kevin Harrington described the results as "a potential game changer for head and neck cancer, introducing a new drug treatment into our armoury that at last is better than standard chemotherapy." He said once the disease has "relapsed or spread, head and neck cancer is extremely difficult to treat, with surgery and radiotherapy often impossible, so it's very good news for patients that these interim results indicate we now have a new treatment that works, and can significantly extend life."
Nick Botwood, therapeutic area development lead at Bristol-Myers Squibb, said the company plans to study Opdivo earlier in the disease and in combination with other drugs. "This is the tip of the iceberg," he remarked, adding "our mind is very much on tomorrow, and what we can do in the future to bring treatment options to a wider range of patients." However, Lillian Siu, co-chair of the AACR's clinical trial committee, suggested it will be important to find a biomarker to identify which patients are most likely to benefit from the treatment, which costs about $150 000 a year. Conventional indicators such as disease progression did not help identify who would respond to Opdivo, with Siu noting the drug did not seem to slow the growth of tumours in the study, even though patients had better survival rates.
Opdivo was initially awarded accelerated approval by the FDA in 2014 for unresectable or metastatic melanoma, and later expanded to include monotherapy for patients with previously untreated BRAF V600 wild-type unresectable or metastatic melanoma. The drug is also approved in the US for squamous and non-squamousnon-small-cell lung cancer (NSCLC), as well as for metastatic renal cell carcinoma in patients who previously received anti-angiogenic therapy.
Meanwhile, Merck & Co. recently announced that its anti-PD-1 therapy Keytruda (pembrolizumab) received a priority review for head and neck cancer from US regulators, with a decision expected by August 9.
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