The safety and efficacy of MPDL3280A combined with platinum-based chemotherapy in the treatment of advanced non-small cell lung cancer

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MPDL3280A, which retains the PD-L2 / PD-1 interaction, potentially reduces autoimmune lung toxicity, and has a good effect on advanced NSCLC. Platinum-based chemotherapy is still the standard first-line treatment for non-small cell lung cancer, with a historical overall effective rate of about 30%. Preclinical data indicate that chemotherapy may promote the release of tumor antigens and enhance MPDL3280A activity. Therefore, we study MPDL3280A + chemotherapy for non-small cell lung cancer patients without chemotherapy.

Research methods:

The study evaluated MPDL3280A in combination with carboplatin + paclitaxel (ARM C), pemetrexed (ARM D), or weekly paclitaxel (Arm E) to treat locally advanced or metastatic non-small cell lung cancer without chemotherapy.

The patient received intravenous MPDL3280A 15 mg / kg once every three weeks and the standard chemotherapy dose was 4-6 times. MPDL3280A was used for maintenance therapy until disease progression. The unproven effective remission rate was evaluated on June 29, 2014 (data as of September 29, 2014).

PD-L1 expression was detected using SP142 antibody immunohistochemistry. Results: Safety assessment of 37 patients

Divided into three groups:

Group C: Atezolizumab + carboplatin + paclitaxel, 8 patients;

Group D: Atezolizumab + carboplatin + pemetrexed, 14 patients;

Group E: Atezolizumab + carboplatin + protein-binding paclitaxel, 15 patients.

54% of the crossover group were men, with a median age of 65 years (range, 40-82 years). 81% of patients are non-squamous cell carcinoma, and 19% are patients with squamous cell carcinoma. The patient received Atezolizumab 15mg / kg and standard chemotherapy for 4-6 cycles, and then continued MPDL3280A single drug until disease progression.

The average follow-up time was 154 days (range, 1-346 days).

The most common side effects associated with chemotherapy in the crossover group, such as nausea (CD group, 50%; group E, 73%)), fatigue (group C, 38%; group D, 36%; group E, 73%), constipation (Group C, 25%; Group D, 71%; Group E, 27%).

Common side effects of MPDL3280A: anemia (D & E group, 7%), neutropenia (C group, 13%; D group, 7%), thrombocytopenia (D & E group, 7%). No patient developed pneumonia.

As a result of the increase in neutropenia, a patient in group D developed MPDL3280A-associated G5 symptoms of candidaemia.

Finally, the effect of 30 patients was evaluated: the total ORR was 67%, 60% in group C, 75% in group D, and 62% in group E. The good news is that the treatment effect has nothing to do with the expression of PDL1.

The previously announced treatment effect of MPDL3280A on NSCLC requires patients to have PDL1 expression, and ORR increases as PD-L1 expression increases.

Therefore, the results of this trial are very meaningful for most NSCLC patients, meaning that most patients with advanced NSCLC can be treated by this method.

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