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Patients with previously treated advanced lung cancer lived about 6 months longer if they received a PD-1 inhibitor instead of chemotherapy, a large randomized study from China showed.

Median overall survival (OS) was 17.2 months with tislelizumab and 11.9 months with docetaxel. In the prespecified subgroup with PD-L1 expression ≥25%, tislelizumab led to a median OS of 19.1 months versus 11.9 months with chemotherapy. OS at 12 and 24 months was substantially higher among patients treated with the PD-1 inhibitor.

Progression-free survival (PFS), overall response rate (ORR), and duration of response (DOR) all improved significantly with tislelizumab, reported Caicun Zhou, MD, of Shanghai Pulmonary Hospital, at the American Association for Cancer Research virtual meeting.

"Tislelizumab monotherapy in second- and third-line non-small cell lung cancer [NSCLC] showed consistent benefit over docetaxel across all PD-L1 expression subgroups," Zhou concluded. "Tislelizumab had a tolerable and manageable safety profile consistent with other PD-1/L1 inhibitors, with a lower incidence of greater than or equal to grade 3 adverse events than docetaxel."

A randomized trial of a different PD-1 inhibitor developed in China also showed improvement in OS and PFS as second-line therapy for locally advanced/metastatic NSCLC. Patients treated with sintilimab had a median OS of 11.79 months versus 8.25 months with docetaxel, reported Yuankai Shi, MD, of the National Cancer Center and Chinese Academy of Medical Sciences & Peking Union Medical College in Beijing.

Questions about Generalizability

During a discussion that followed the presentations, several questions from the virtual audience pertained to the applicability of the findings outside of China. In the U.S., and many other parts of the world, PD-1/L1 inhibitors have already moved into first-line therapy, whereas chemotherapy remains the first-line standard in China.

"We had a global CIO [chief information officer] to manage the study," said Shi. "We performed an interim analysis, and the benefit was comparable between the Chinese population and the Caucasian population."

Members of the audience also noted that the results with tislelizumab, in particular, in second and third line appeared superior to outcomes of second- and third-line therapy in U.S.-based trials. The questioners wondered whether the differences might have been related to differences in patients or study populations.

"I do think our study has the better efficacy compared with other randomized phase III trials ... ," said Shi, who addressed questions for both studies because Zhou was unable to participate in the discussion. "We had a long progression-free survival and overall survival. I do think that tislelizumab has a special structure that is engineered to minimize the binding on the macrophage. As you know, the macrophage may be responsible for HPD [hyperprogessive disease] in lung cancer."

"When we look at the survival curves, they did not cross in our study compared with others," Shi noted. "I do think that compound will be approved in China and will be approved in other countries. The compound is good and should be the kind of standard care in the second-line setting."

Bevacizumab (Avastin) plus chemotherapy is standard first-line therapy in China for squamous-cell NSCLC and has led to outcomes comparable to those attained with an anti-PD-1/L1 agent plus chemotherapy in the first-line setting, Shi continued. After failure of first-line bevacizumab-chemotherapy, tislelizumab would be a good second-line option.

Key Trial Results

Zhou reported findings from the phase III , which included patients with locally advanced/metastatic NSCLC, disease recurrence, or progression during or after platinum-containing chemotherapy, no more than two prior lines of systemic therapy, and no known EGFR or ALK mutations. They were randomized 2:1 to tislelizumab or docetaxel, and treatment continued until disease progression or unacceptable toxicity.

The trial had dual primary endpoints of OS in the intention-to-treat (ITT) population and in patients with PD-L1 expression ≥25% (PD-L1-high). Data analysis included 805 patients (172 in the PD-L1-high subgroup) with a median follow-up of 19 months.

The ITT analysis showed a 36% reduction in the survival hazard in favor of tislelizumab (95% CI 0.53-0.78, P<0.0001). OS at 12 and 24 months was 61.9% and 39.4% with tislelizumab versus 49.8% and 25.0% with chemotherapy. In the subgroup with high PD-L1 expression, improvement in the survival hazard increased to 48% (95% CI 0.38-0.71, P<0.0001). The 12- and 24-month survival was 67.5% and 44.7% with tislelizumab versus 49.1% and 24.5% with docetaxel.

Tislelizumab led to a median PFS of 4.1 months versus 2.6 months with chemotherapy. ORR was 21.9% with tislelizumab and 7.1% with docetaxel. Disease control rates were 55.7% with tislelizumab and 47.2% with docetaxel. DOR was more than twice as long with tislelizumab (13.5 vs 6.2 months).

Rates of all-grade treatment-emergent adverse events (TEAEs) were similar between treatment arms, but treatment-related adverse events (TRAEs) occurred less frequently with tislelizumab (73% vs 93.8%). Grade ≥3 TEAEs (38.6% vs 74.8%) and TRAEs (14.4% vs 66.3%) also occurred less often with the anti-PD-1 therapy.

The phase III randomized evaluated sintilimab as second-line therapy for squamous-cell NSCLC that progressed during or after platinum-based chemotherapy. Data analysis included 290 patients randomized to single-agent sintilimab or docetaxel. The primary endpoint was OS.

After a median follow-up of 23.56 months, data analysis showed a 26% reduction in the survival hazard in favor of the anti-PD-1 antibody (95% CI 0.56-0.96, P=0.02489). Median PFS also was significantly prolonged with sintilimab (4.3 vs 2.79 months, P<0.00001). ORR was 25.5% with sintilimab and 2.2% with docetaxel.

Rates of all-grade TRAEs were similar in the two treatment groups (83-85%). Grade ≥3 TRAEs occurred less frequently with sintilimab (18.1%) than with docetaxel (36.2%).