Dr. Gandhi said it’s likely that other PD1 inhibitor chemotherapy combinations may provide similar benefits, as shown in IMpower150 (ClinicalTrials.gov Identifier: NCT02366143), which evaluated the efficacy of atezolizumab plus bevacizumab and chemotherapy, finding a clinically meaningful PFS benefit in all patients, including those with EGFR/ALKgenomic alterations who were previously treated with targeted therapy.3

“There’s a lot more to be figured out about how and why these combinations are working together,” she said. KEYNOTE-189 was really a purely clinical study that quickly combined the drugs.” More research is needed in terms of sequencing and analyzing the drugs to determine what is actually happening in serial biopsies,” she said. “We need to build our base of knowledge from where we are now.”

Pembrolizumab and Chemotherapy In The Clinic 


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What KEYNOTE-189 did not address was whether the combination of pembrolizumab chemotherapy is superior to pembrolizumab alone, which still may be good option for patients with 50% or greater PD-L1 expression.

“There are multiple options for clinicians and their patients. But chemotherapy alone is no longer one of them,” she said.

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To date, there is no data on sequencing with pembrolizumab and pemetrexed and a platinum-based drug, but KEYNOTE-24 and KEYNOTE-189 both suggest that early introduction of immunotherapy “may be important given the dramatic survival differences in both studies despite crossover to immunotherapy in the second line. I would be hesitant to extrapolate this regimen to other contexts or other combinations. That would not be evidence-based medicine,” she said.

There was a slightly higher risk of kidney toxicity in the pembrolizumab group, but all PD-1 and PD-L1 inhibitors affect the kidney, Dr Gandhi added. The rate of serious acute kidney injury “was still only 2%.”

What the Future Holds

While it is clear pembrolizumab and chemotherapy are highly effective in patients with NSCLC, researchers still need to determine if the combination is more superior to pembrolizumab alone in the high PD-L1 expressors. 

“What emerged from all the presented studies was that chemotherapy alone is no longer a standard of care for nonsquamous NSCLC, and that the backbone of therapy is immunotherapy in some form,” Dr Gandhi concluded. “Whether it’s immunotherapy on its own, in combination with other immunotherapies, or in combination with chemotherapy has not yet been addressed. Our study clearly demonstrated its benefits for all patients, so it could be used in all patients. Clinicians will now have the ability for more nuanced decision making.”

References

  1. Gandhi L, Rodriguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small cell lung cancerN Engl J Med. doi: 10.1056/NEJMoa1801005
  2. Hellmann MD, Ciuleanu T, Pluzanski A, et al. Nivolumab (nivo) + ipilimumab (ipi) vs platinum-doublet chemotherapy (PT-DC) as first-line (1L) treatment (tx) for advanced non-small cell lung cancer (NSCLC): initial results from CheckMate 227. Presented at: American Association for Cancer Research Annual Meeting 2018; April 16, 2018: Chicago, IL.
  3. Kowantz M, Socinski MA, Zou W, et al. IMpower150: Efficacy of atezolizumab (atezo) plus bevacizumab (bev) and chemotherapy (chemo) in 1L metastatic nonsquamous NSCLC (mNSCLC) across key subgroups. Presented at: American Association for Cancer Research Annual Meeting 2018; April 16, 2018: Chicago, IL.