Atezolizumab plus bevacizumab plus carboplatin plus paclitaxel (ABCP) is a promising regimen for patients with previously treated epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC), safety and efficacy results of a phase II study display. Physician’s Weekly interviewed Dr. Naoki Furuya (Ohio State University, OH, USA), first author of this trial, to discuss the impact of this study and the future of ABCP in the EGFR-mutated NSCLC population [1]. These data were presented at the American Society of Clinical Oncology (ASCO) 2022 Annual meeting, which was held 3-7 June 2022, in Chicago, IL.

A recent subgroup analysis of the IMpower150 trial (NCT02366143) indicated that patients with EGFR-mutated NSCLC may benefit from ABCP [2]. Therefore, Dr. Furuya and co-investigators designed the single-arm multicentre phase II NEJ043 study (031190066).

to evaluate the efficacy and safety of ABCP in patients with non-squamous EGFR-mutated NSCLC who had received prior EGFR tyrosine kinase inhibitors. In total, 60 patients were included in the study. All participants received a combination of 1200 mg atezolizumab, 15 mg/kg bevacizumab, 6 mg/mL/min carboplatin AUC, and 175 mg/m^2 ­­paclitaxel, every 3 weeks, for up to 4 cycles. Hereafter they continued on atezolizumab and bevacizumab until the clinical benefit was lost. The primary endpoint was progression-free survival (PFS) by extramural review.

After a median follow-up of 12.8 months, the median PFS was 7.4 months (95% CI 5.7-8.2 months). Furthermore, the median overall survival (OS) of the study population was 18.9 months (95% CI 13-not reached). Next, Dr. Furuya and colleagues reported a confirmed overall response rate by extramural review of 56% (95% CI 43-69).  Also, patients with EGFR T790M mutations may benefit more from ABCP than those without T790M mutations, PFS results showed (8.1 months vs 6.8 months).

ABCP was generally well tolerated in the study population, according to Dr. Furuya and his team. Grade 3 or higher adverse events (AEs) were observed in 92% of the patients, most commonly being neutropoenia events (63%). Interstitial lung disease was reported in 2% of the patients. Finally, in 12% of the patients, AEs led to treatment discontinuation.

Physician’s Weekly spoke with Dr. Furuya to follow up on some questions:

Why did you perform this study? What was the rationale?

We conducted a phase 2 study to investigate atezolizumab plus bevacizumab plus carboplatin plus paclitaxel for drug combination treatment for patients with EGFR-mutated non-small cell lung cancer. The current standard treatment for EGFR-mutated non-small cell lung cancer is tyrosine kinase inhibitor monotherapy.

However, after a patient progresses while on a tyrosine kinase inhibitor, systemic immunotherapy is not effective for EGFR mutation non-small cell lung cancer. There is a clear unmet need for effective immunotherapy, so we conducted phase 2 study to investigate this 4 drug combination treatment.

What were the characteristics of the patients involved?

All patients were previously treated with EGFR-TKI and most of patients were never-smokers or they were former smokers. Female patients were dominant. Around 50% of patients were treated with osimertinib and 30% of patients after trial were put on a second-generation EGFR-TKI.

What can you tell me about the results?

The primary endpoint of this trial is progression-free survival. The median progression-free survival was 7.4 months and immature median overall survival was 18.9 months. Importantly, the response rate is 56%. The response rate and the progression-free survival rate is relatively higher than previous standards of care. Still, of course, we have to be careful when making comparisons with historical data. Although the progression-free survival looks pretty good here, the most important piece of data we are waiting on is to see an improvement in duration of response for immunotherapy, for the atezolizumab. We hope that this will make a unique distinction.

Do you think that this data is sufficient to progress to a phase 3 trial?

Yes. But this trial is still immature, especially in survival, but the progression-free survival looks promising and would warrant further investigation in a phase 3 setting.

And how long will you follow these patients?

We will be following these patients to determine the survival rate; we expect that to be at 2 or 3 years, depending on the number of events.

Were the safety signals just consistent with the 4 drugs individually? Or did you see additional safety signals?

We did not observe any new toxicity signals. But in this study, however, febrile neutropenia developed in over 30% of the patients, which is of course significant. Nevertheless, the febrile neutropenia was manageable, and there were no serious AEs as a result. There were no deaths in this cohort.

Take-home message?

We can conclude from these initial phase 2 data that this combination therapy might be promising for EGFR-mutation positive non-small cell lung cancer. The safety profile showed acceptable tolerability and no serious toxicities.