三代EGFR抑制剂和PD-1实验结果公布(ASCO 2015摘要)

昨天美国的临床癌症学会公布了这个月底大会的摘要。
不少药厂选择这个大会公布他们临床实验大致的结果，具体数据要等到五月底大会才知道。

Roche PD-1的结果很好，说是在PD L1+的人群有效， PD-L1没有表达的人群无效
Merck的Keytruda对NSCLC的有效率是20-25%
Opvido的结果还没有看。

大家可以把找到的论文摘要贴上来，一起翻译一下。

Roche的PD-1

A mid-stage trial of Roche Holding AG's experimental immunotherapy showed that it doubled the likelihood of survival for lung cancer patients with the highest levels of a specific biomarker.

The drug, known by the code name MPDL3280A, is part of a new class designed to help the body's immune system fend off cancer by blocking a protein known as Programmed Death receptor (PD-1), or a related target known as PD-L1, used by tumors to evade the body's defenses.

Unlike some of its competitors, Roche is using its own assay to measure patient levels of PD-L1 in order to identify people most likely to benefit from the treatment.

Interim results from the trial of 287 patients with previously treated non-small cell lung cancer showed that the immunotherapy reduced the risk of death by 53 percent in those with the highest levels of the biomarker, compared with those treated by chemotherapy.
Improved survival was also seen in patients who had lower levels of PD-L1, although the difference was not as dramatic.

"The greater the expression of PD-L1, the greater the benefit," said Sandra Horning, chief medical officer at Roche's Genentech unit. "That's what exciting to us - seeing this biology that we've been studying really intently playing out in the clinic."

The update was provided in a scientific summary, or abstract, released on Wednesday ahead of the annual meeting of the American Society of Clinical Oncology (ASCO) later this month.

The immunotherapy, an antibody, was described as generally well tolerated. More patients on the drug experienced respiratory events, but chemotherapy was associated with a higher overall rate of adverse side effects.

MPDL3280A, which is being studied for treatment of a range of different cancer types, has been granted "breakthrough therapy" status by the U.S. Food and Drug Administration.

AZD9291:
AstraZeneca updates on immuno-oncology pipeline and combination treatments at ASCO 2015

•61 data abstracts - with 6 oral presentations - to be featured from across AstraZeneca’s broad pipeline, including in lung, ovarian and breast cancers.
•Increased confidence in the potential of anti-PD-L1 MEDI4736 as a cornerstone for combination treatments with other immuno-oncology and small molecule investigational medicine.
•Updated data will be presented on the safety and clinical activity of MEDI4736 + tremelimumab in patients with NSCLC.
•Data will also be presented on the safety of MEDI4736 in combination with EGFR inhibitors gefitinib and AZD9291, as well as the triple combination with trametinib (MEK inhibitor) + dabrafenib (BRAF inhibitor)1.
•In small molecule combinations, data will be presented on AZD9291 with savolitinib (cMET inhibitor) or selumetinib (MEK inhibitor), being investigated as potential treatments for overcoming newly-identified forms of resistance in EGFR mutated lung cancer.

Selected Important Safety Information for KEYTRUDA

Pneumonitis occurred in 12 (2.9%) of 411 patients with advanced melanoma receiving KEYTRUDA (the approved indication in the United States), including Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%) patients, respectively. Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 pneumonitis.

Colitis (including microscopic colitis) occurred in 4 (1%) of 411 patients, including Grade 2 or 3 cases in 1 (0.2%) and 2 (0.5%) patients respectively, receiving KEYTRUDA. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Hepatitis (including autoimmune hepatitis) occurred in 2 (0.5%) of 411 patients, including a Grade 4 case in 1 (0.2%) patient, receiving KEYTRUDA. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hypophysitis occurred in 2 (0.5%) of 411 patients, including a Grade 2 case in 1 and a Grade 4 case in 1 (0.2% each) patient, receiving KEYTRUDA. Monitor for signs and symptoms of hypophysitis. Administer corticosteroids for Grade 2 or greater hypophysitis. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3; and permanently discontinue KEYTRUDA for Grade 4 hypophysitis.

Nephritis occurred in 3 (0.7%) patients receiving KEYTRUDA, consisting of one case of Grade 2 autoimmune nephritis (0.2%) and two cases of interstitial nephritis with renal failure (0.5%), one Grade 3 and one Grade 4. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

Hyperthyroidism occurred in 5 (1.2%) of 411 patients, including Grade 2 or 3 cases in 2 (0.5%) and 1 (0.2%) patients respectively, receiving KEYTRUDA. Hypothyroidism occurred in 34 (8.3%) of 411 patients, including a Grade 3 case in 1 (0.2%) patient, receiving KEYTRUDA. Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer corticosteroids for Grade 3 or greater hyperthyroidism. Withhold KEYTRUDA for Grade 3; permanently discontinue KEYTRUDA for Grade 4 hyperthyroidism. Isolated hypothyroidism may be managed with replacement therapy without treatment interruption and without corticosteroids.

Other clinically important immune-mediated adverse reactions can occur. The following clinically significant, immune-mediated adverse reactions occurred in less than 1% of patients treated with KEYTRUDA: exfoliative dermatitis, uveitis, arthritis, myositis, pancreatitis, hemolytic anemia, partial seizures arising in a patient with inflammatory foci in brain parenchyma, adrenal insufficiency, myasthenic syndrome, optic neuritis, and rhabdomyolysis.

For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement of the adverse reaction to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Restart KEYTRUDA if the adverse reaction remains at Grade 1 or less. Permanently discontinue KEYTRUDA for any severe or Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

Based on its mechanism of action, KEYTRUDA may cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

For the treatment of advanced melanoma, KEYTRUDA was discontinued for adverse reactions in 6% of 89 patients who received the recommended dose of 2 mg/kg and 9% of 411 patients across all doses studied. Serious adverse reactions occurred in 36% of patients receiving KEYTRUDA. The most frequent serious adverse drug reactions reported in 2% or more of patients were renal failure, dyspnea, pneumonia, and cellulitis.

The most common adverse reactions (reported in ≥20% of patients) were fatigue (47%), cough (30%), nausea (30%), pruritus (30%), rash (29%), decreased appetite (26%), constipation (21%), arthralgia (20%), and diarrhea (20%).

The recommended dose of KEYTRUDA is 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity. No formal pharmacokinetic drug interaction studies have been conducted with KEYTRUDA. It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA. Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

pd-1表达怎么做

可以搜“PD1抗体抗癌指南民间版” 里面有讲