Advanced Squamous NSCLC Survival Improved With Chemoimmunotherapy Regardless of PD-L1 Expression

Adam J. Schoenfeld, MD

Medical Oncologist

Memorial Sloan-Kettering Cancer Center

New York, NY

Targeted Oncology^TM: Please describe the study design and goals of the KEYNOTE-407 trial (NCT02775435) for patients with advanced squamous cell non–small cell lung cancer (NSCLC).

SCHOENFELD: This is a [trial of] first-line chemotherapy with or without pembrolizumab [Keytruda] in stage IV squamous NSCLC. This study randomly assigned patients to 200 mg of pembrolizumab every 3 weeks with carboplatin and paclitaxel or nab-paclitaxel for 4 cycles versus only carboplatin and paclitaxel or nab-paclitaxel for 4 cycles. The primary end points were progression-free survival [PFS] and overall survival [OS], and the secondary end points were objective response rate, duration of response, and safety.

What were the findings for OS and PFS in this study?

Data were presented from the second interim analysis on OS and PFS. The OS had a hazard ratio of 0.64 [95% CI, 0.49-0.85; P = .0008] in favor of the pembrolizumab plus chemotherapy group, and a median OS of 15.9 months [95% CI, 13.2-not estimable] versus 11.3 months [95% CI, 9.5-14.8] for patients who received chemotherapy alone.¹ The median PFS for pembrolizumab plus chemotherapy was 6.4 months [95% CI, 6.2-8.3] versus 4.8 [95% CI, 4.3-5.7] months for chemotherapy alone, with a hazard ratio of 0.56 [95% CI, 0.45-0.70; P < .0001] significantly in favor of pembrolizumab plus chemotherapy as well.

What was reported about the subgroup analyses of the primary end points, especially PD-L1 score?

OS subgroup analyses took into account age, sex, performance status, region of enrollment, tumor proportion score/PD-L1 score, as well as the 2 different taxane-based regimens. For pretty much all of the groups, the pembrolizumab combination was favored for OS.

[There were data for] tumor PD-L1 expression subgroups in PD-L1–negative, PD-L1–low, and PD-L1–high patients. Again, there was a separation of the Kaplan-Meier curve favoring pembrolizumab plus chemotherapy in all groups. One caveat to mention is that the number of patients with a PD-L1 score of 50% or greater was lower than the other 2 groups, and so the confidence interval crossed 1.00; you have to take into account the number of patients in that group.

But otherwise, for patients with PD-L1–negative expression or positive expression of 1% to 49%, pembrolizumab plus chemotherapy was significantly associated with better OS. The median OS for patients with [negative PD-L1 expression who received pembrolizumab] was 15.9 months versus [10.2] months for patients who didn’t receive pembrolizumab. We saw something similar for PD-L1–low versus PD-L1–negative, where we’re seeing a better survival among the patients who have negative PD-L1 expression. For the PD-L1–low group, median OS is 14.0 months with pembrolizumab versus 11.6 months [for chemotherapy alone]. Median OS was not reached for [either arm for] the PD-L1–high group.

[Looking at] PFS by PD-L1 expression subgroup, PD-L1–negative patients had superior outcomes with pembrolizumab plus chemotherapy compared with chemotherapy alone, with a median PFS of 6.3 months for pembrolizumab versus 5.3 motnhs with chemotherapy for patients with PD-L1 expression of 1% to 49%. The median PFS was 7.2 months for those who received pembrolizumab versus 5.2 for chemotherapy. Then for patients who had greater than 50% PD-L1 expression, it’s 8.0 months for pembrolizumab versus 4.2 months for chemotherapy.

How did the toxicity of the KEYNOTE-407 regimen affect patients?

The [investigators reported on] all-cause adverse events [AEs] occurring in at least 20% of patients as well as immune-mediated AEs and infusion reactions. Hypothyroidism was the most common immune-mediated AE, in [7.9% of] the pembrolizumab plus chemotherapy group.² There was also some hyperthyroidism at [7.2%], pneumonitis [in 6.5%], colitis occurring in [2.5%] followed by hepatitis in [1.8%], and skin reactions [in 1.8%]. Then are hypophysitis [and thyroiditis each occurring in 1.1% of patients], and nephritis occurring in 0.7% of patients.

_References:

_{1. Paz-Ares L, Luft A, Vicente D, et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med. 2018;379(21):2040-2051. doi:10.1056/NEJMoa1810865}

_{2. Paz-Ares LG, Luft A, Tafresh 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(15_suppl):105-105. doi:10.1200/JCO.2018.36.15_suppl.105}