Last year saw many important advances in new medications that can lead to a benefit and hopefully a cure for more patients. I'm

going to highlight the top five developments of this year.

Number five is the emergence of the antibody drug conjugates (ADCs). Years ago, my colleague, Bob Li, showed how adotrastuzumab emtansine was helpful for persons with lung cancers with HER2 mutations. This year he showed that another ADC,

trastuzumab deruxtecan, was even more helpful for these patients. Other agents of this class are moving forward as a construct.

The ADCs are going to become more and more important.

The next extremely important development was the approval of at least three medications for targets for which we previously didn't have drugs. For endothelial growth factor receptor (EGFR) exon 20 insertions, we now have amivantamab and mobocertinib, and for KRAS G12C we have sotorasib. We always believed we would have therapies for these targets, and we were close, but not there. Now we're there.

The third most important development was reported by Patrick Forde at the American Association for Cancer Research meeting. He and his colleagues looked at neoadjuvant chemotherapy plus nivolumab, comparing this with chemotherapy alone.

They found a clear response benefit from the three drugs over chemo alone and a higher rate of pathologic complete response,

the main goal of the trial. A press release published after the presentation reported an association between the treatment with nivolumab plus chemotherapy over chemo alone in improving disease-free survival. Here, three cycles of therapy before treatment, with no adjuvant therapy , led to an improvement in disease-free survival. Hopefully a paper and an FDA approval will follow that.

The second most important development this year was the use of adjuvant atezolizumab in patients with resected non-small cell lung cancer (NSCLC). This was reported at the American Society of Clinical Oncology meeting. There, patients with stages II to

IIIA and programmed death-ligand 1 (PD-L1) greater than 1%, had a significant and dramatic improvement in progression free survival, with the addition of atezolizumab, and it's become a new standard of care. [Editor’s note: The improvement was in disease-free survival, as opposed to progression-free survival.] It's been approved by the FDA, and quickly included in guidelines.

In addition to osimertinib for patients with EGFR mutations after chemotherapy and after curative surgery, we now have atezolizumab for patients with PD-L1 staining 1% or greater who have a complete resection. I should also mention that these things are mutually exclusive. The patients who have targets such as EGFR do not achieve the degree of benefit that patients who do not have a gene target achieve. Thus, it's important to test patients to find gene targets for those who could benefit from drugs like [osimertinib], and conversely, for those who don't have a target, to quickly make sure they get atezolizumab.

The most dramatic development this year is that we have finally hit the 50% percent level, rounding up a bit, of the proportion of patients with mutant cancers that have a gene target. People have said, "Oh, only a few percent of patients have gene targets, but when you add all those percentages up, we're near 50%." This highlights the importance of testing and the importance of

matching those targeted therapies to the gene targets that are found in patient's tumors. Now we are able to find a target that leads to therapy in nearly half the patients.

This was a very good year of developments all through the spectrum of care, from early to late-stage illnesses, with clear benefits from the new therapies, and a lot of hope that this wave of research will continue and lead to even more benefits next year.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. His research interests include targeted therapies for lung cancer, multimodality therapy, the development of new anticancer drugs, and symptom management with a focus on preventing emesis.

Follow Medscape on Facebook, Twitter, Instagram, and YouTube

Medscape Oncology © 2022 WebMD, LLC

Top 5 Developments in Lung Cancer in 2021

‍