Atezolizumab Regimen Extends PFS in Frontline Nonsquamous NSCLC

Sandra Horning, MD

Adding atezolizumab (Tecentriq) to pemetrexed (Alimta) and cisplatin or carboplatin in the frontline setting reduced the risk of disease progression or death versus chemotherapy alone in patients with advanced nonsquamous non—small cell lung cancer (NSCLC), according to findings from the phase III IMpower132 study.

Genentech (Roche), the manufacturer of atezolizumab, noted in a press release that the results at the interim analysis did not demonstrate a statistically significant improvement in overall survival (OS), the coprimary endpoint of the trial. However, there was a numerical OS improvement in the atezolizumab arm, and survival data from the ongoing study are anticipated to report out next year.

“The IMpower132 study showed Tecentriq plus chemotherapy prolonged the time people with this type of advanced lung cancer lived without their disease worsening. We will discuss these results with health authorities,” Sandra Horning, MD, chief medical officer and head of Global Product Development, Genentech, said in a statement.

In a comment posted today on Twitter, H. “Jack” West, MD, thoracic oncologist, Swedish Cancer Institute at Swedish Medical Center, said that the IMpower132 trial had a “similar design as KEYNOTE-189, achieving PFS but not OS benefit (at least not yet). Comparing to [KEYNOTE]-189, IMpower132 falls short [without] OS benefit.”

The double-blind phase III KEYNOTE-189 study accrued 616 patients with advanced or metastatic nonsquamous NSCLC, regardless of PD-L1 expression. Patients were not EGFR- or ALK-positive, and had not received systemic therapy for advanced disease. The trial randomization was 2:1 in favor of the pembrolizumab arm.

At a median follow-up of 10.5 months, the estimated 12-month OS rate was 69.2% (95% CI, 64.1-73.8) in the pembrolizumab arm compared with 49.4% (95% CI, 42.1-56.2) in the control group (HR, 0.49; 95% CI, 0.38-0.64; P <.001).¹

The median OS was not reached in the pembrolizumab cohort, compared with 11.3 months (95% CI, 8.7-15.1) in the chemotherapy-alone arm. The OS benefit was observed, irrespective of PD-L1 status. The study also met the coprimary endpoint of progression-free survival (PFS), with a median PFS of 8.8 months (95% CI, 7.6-9.2) in the pembrolizumab group versus 4.9 months (95% CI, 4.7-5.5) in the control arm (HR, 0.52; 95% CI, 0.43 to 0.64; P <.001).

West also noted in his Twitter post that the IMpower132 findings are, “Similar to results seen on IMpower131 vs. [KEYNOTE]-407. May be efficacy [difference], but I wonder if [differences] in crossover rates could explain.”

Data from the phase III IMpower131 trial presented at the 2018 ASCO Annual Meeting showed that the addition of atezolizumab to frontline carboplatin and nab-paclitaxel (Abraxane) delayed the risk of progression or death by 29% compared with chemotherapy alone for patients with advanced squamous NSCLC.²

At a median follow-up of 17.1 months, the median PFS was 6.3 months (95% CI, 5.7-7.1) with the addition of atezolizumab versus 5.6 months (95% CI, 5.6-5.7) with chemotherapy alone (HR, 0.71; 95% CI, 0.60-0.85; P = 0.0001). The 12-month PFS rates were 24.7% versus 12.0%, respectively.

At the first interim OS analysis, the median OS was 14.0 months (95% CI, 12.0-17.0) with the atezolizumab triplet compared with 13.9 months (95% CI, 12.3-16.4) with chemotherapy alone (HR, 0.96; 95% CI, 0.78-1.18; P = 0.6931). The 12- and 24-month OS rates were 55.6% versus 56.9% and 31.9% versus 24.1%, respectively. The OS follow-up is continuing, with another analysis anticipated later this year.

Data were also presented at the 2018 ASCO Annual Meeting from the phase III KEYNOTE-407 trial, in which adding pembrolizumab to frontline carboplatin/paclitaxel or nab-paclitaxel reduced the risk of death by 36% compared with chemotherapy alone in patients with metastatic squamous NSCLC.³

The median OS was 15.9 months (95% CI, 13.2 — not evaluable) with pembrolizumab versus 11.3 months (95% CI, 9.5-14.8) with chemotherapy alone (HR, 0.64; 95% CI, 0.49-0.85; P = .0008. The OS benefit was observed regardless of PD-L1 expression level, choice of taxane, age, sex, and ECOG performance status.

Progression-free survival was also improved with the addition of pembrolizumab. The median PFS was 6.4 months (95% CI, 6.2-8.3) with the PD-1 inhibitor compared with 4.8 months (95% CI, 4.3-5.7) with chemotherapy alone (HR, 0.56; 95% CI, 0.45-0.70; P <.0001). While the PFS benefit was also observed across all PD-L1 expression levels, there was a correlation between an increase in PD-L1 level and a greater magnitude of benefit.

References

1. Gandhi L, Rodgríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non—small-cell lung cancer [published online April 16, 2018]. N Engl J Med. doi: 10.1056/NEJMoa1801005.
2. Jotte RM, Cappuzzo F, Vynnychenko I, et al. IMpower131: Primary PFS and safety analysis of a randomized phase III study of atezolizumab + carboplatin + paclitaxel or nab-paclitaxel vs carboplatin + nab-paclitaxel as 1L therapy in advanced squamous NSCLC. J Clin Oncol. 2018;36 (suppl; abstr LBA9000).
3. Paz-Ares LG, Luft A, Tafreshi A, et al. Phase 3 study of carboplatin-paclitaxel/nab-paclitaxel (Chemo) with or without pembrolizumab (Pembro) for patients (Pts) with metastatic squamous (Sq) non-small cell lung cancer (NSCLC). J Clin Oncol. 2018;36 (suppl; abstr 105).

The FDA approved single-agent atezolizumab in October 2016 for the treatment of patients with metastatic NSCLC who have progressed after a platinum-containing regimen and an FDA-approved targeted therapy for those patients harboring EGFR or ALK abnormalities.

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The open-label phase III IMpower132 trial randomized 578 chemotherapy-naïve patients with advanced nonsquamous NSCLC in a 1:1 ratio to receive pemetrexed with cisplatin or carboplatin (investigator’s choice) alone or in combination with atezolizumab. Following the induction phase, patients with a clinical benefit initiated maintenance therapy. In the experimental arm, maintenance therapy consisted of atezolizumab and pemetrexed, while those in the control arm received maintenance pemetrexed alone.