FDA OKs First-Line Immunotherapy Combo for Mesothelioma

The FDA on Friday approved dual checkpoint blockade with nivolumab (Opdivo) plus ipilimumab (Yervoy) for the first-line treatment of unresectable malignant pleural mesothelioma.

Support for the approval was based on findings from CheckMate 743, an open-label phase III trial that randomized 605 patients with unresectable malignant pleural mesothelioma to either standard platinum-based chemotherapy or the PD-1 inhibitor nivolumab (360 mg every 3 weeks) in combination with the anti-CTLA-4 drug ipilimumab (1 mg/kg every 6 weeks).

“Malignant pleural mesothelioma is a rare cancer with limited treatment options. When it is diagnosed in advanced stages, the five-year survival rate is approximately 10 percent,” said investigator Anne Tsao, MD, of MD Anderson Cancer Center in Houston, in a press release from drugmaker Bristol-Myers Squibb. “The survival results from the CheckMate-743 trial show that the combination of nivolumab and ipilimumab could become a new front-line standard of care option. This is exciting news, instilling hope for patients with this devastating disease and for the healthcare providers who care for them.”

Median overall survival in the study reached 18.1 months with nivolumab-ipilimumab, as compared to 14.1 months with chemotherapy (HR 0.74, 95% CI 0.61-0.89, P=0.002), and survival rates at 2 years were 41% versus 27%, respectively.

“Today’s approval of nivolumab plus ipilimumab provides a new treatment that has demonstrated an improvement in overall survival for patients with malignant pleural mesothelioma,” Richard Pazdur, MD, the top hematology/oncology official at the FDA, said in a statement. “In 2004, FDA approved pemetrexed in combination with cisplatin for this indication, and now patients now have an important, additional treatment option after more than a decade with only one FDA-approved drug regimen.”

Common adverse events (AEs) with the immunotherapy combination (at least 20%) included fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough, and pruritus. Treatment discontinuation due to toxicity occurred in 23%, and about half had dose interruptions. Additionally, 4.7% of patients discontinued ipilimumab alone due to toxicity.

Serious AEs occurred in a little more than half, the most frequent (≥2%) of which were pneumonia, pyrexia, diarrhea, pneumonitis, pleural effusion, dyspnea, acute kidney injury, infusion-related reaction, musculoskeletal pain, and pulmonary embolism. Four patients died due to treatment-related AEs.

Friday’s approval marks the third for nivolumab-ipilimumab as an initial treatment in thoracic cancers, following two recent approvals for metastatic non-small cell lung cancer — in combination with two cycles of chemotherapy for all adult patients, or as a chemotherapy-free option for those expressing PD-L1 (≥1%).

The combination is also approved for the treatment of advanced melanoma, renal cell carcinoma, liver cancer, and for colorectal cancer patients with microsatellite instability-high or mismatch repair-deficient tumors.

Last Updated October 05, 2020

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    Ian Ingram joined MedPage Today in 2018 as Deputy Managing Editor, and covers oncology for the site.

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Immunotherapy drug boosts survival for lung cancer patients

A newly approved drug for the leading form of the number one cancer killer, lung cancer, does improve patient survival, a new study confirms.

The immunotherapy drug Tecentriq, or atezolizumab, was approved earlier this year by the U.S. Food and Drug Administration to treat patients with newly diagnosed non-small cell lung cancers, or NSCLC, which comprise up to 85% of all lung tumors.

Tecentriq targets a protein known as PD-L1 that lies on the surface of tumor cells. Normally, this protein signals the body’s immune system T cells not to attack. However, by targeting PD-L1, Tecentriq unleashes the body’s natural T cells to target and destroy these cancer cells, researchers at Yale Cancer Center explained.

Tecentriq “has already shown excellent activity in patients who progress on frontline chemotherapy, but this study confirmed that the drug is active in selected patients who have not yet received any treatment for lung cancer,” said medical oncologist Dr. Nagashree Seetharamu, who treats lung cancer patients but wasn’t involved in the new study. She practices at Northwell Health Cancer Institute in Lake Success, N.Y.

The new study was funded by Tecentriq’s maker, Genentech, and the results were published this week in the New England Journal of Medicine.

The study included 554 patients with stage 4 metastatic NSCLC tumors. All patients had tumors lacking mutations in the EGFR or ALK genes: As the researchers explained in a Yale news release, tumors with those mutations are better treated with other drugs.

Among 205 patients whose tumors had high cellular expression of PD-L1, the median overall survival was 20 months for those who received Tecentriq versus 13 months for those who received standard platinum-based chemotherapy.

Median progression-free survival — the time from treatment to the disease beginning to worsen — was eight months for patients who received Tecentriq versus five months for those on standard chemotherapy, the researchers found.

“These are exciting results that could be life-changing for many patients,” said study lead author Dr. Roy Herbst. He is chief of medical oncology at the Yale Cancer Center as well as the Smilow Cancer Hospital.

“Lung cancer is the most common cancer worldwide, with more than 1.5 million patients diagnosed each year. Half of patients are diagnosed with metastatic disease, and they could be a candidate for this drug,” Herbst said in the news release.

“Also encouraging is that [Tecentriq] was generally well tolerated,” said Herbst, who is also associate cancer center director for translational research at the Yale Cancer Center in New Haven, Conn. “Side effects for patients were similar to those seen in other trials of the drug, which has been approved for treatments of several types of cancer.”

The trial also assessed how Tecentriq performed among patients with a “high tumor mutational burden,” which means that they had high levels of genetic mutations in scraps of cancer DNA detected in blood tests. In some types of cancers, high mutational burden is tied to better responses to immunotherapy drugs like Tecentriq.

“Among these patients with NSCLC,