It’s Mark Kris from Memorial Sloan Kettering reflecting on the biggest developments from last year. The breakthrough of the last year, based on the amount of data presented and the importance of the data, is chemotherapy. Many folks have tried to relegate chemotherapy to the museum, but last year it came to the forefront.

Let’s start with neoadjuvant therapy. We now have multiple drug approvals for giving a checkpoint inhibitor and neoadjuvant therapy in what one would say is a new standard of care for patients with locally advanced lung cancers who are candidates for surgery. In all those trials, there was a clear improvement in progression-free survival by adding a checkpoint inhibitor to chemotherapy. The cornerstone of this regimen is chemotherapy.

What about adjuvant therapy? One of the most astounding pieces of data last year was in the adjuvant realm. In the trial comparing adjuvant Osimertinib with placebo in patients with EGFR-mutant disease, patients who received chemotherapy in addition to Osimertinib had a 7% improvement in 5-year survival. Patients who had placebo, who got chemotherapy vs didn’t, had a 9% improvement in 5-year survival. Those are huge numbers for that kind of metric, and it happened with chemotherapy.

What about targeted therapies? Again, people were astounded that, by adding chemotherapy to Osimertinib compared with Osimertinib alone, there was a 9-month improvement overall in progression-free survival. The presentation of the data that has been made, the most remarkable piece of data is that, in patients with brain metastases chemotherapy on top of Osimertinib improved progression-free survival. Not only did it improve progression-free survival, but it did it with brain metastases, where people think it just doesn’t help at all.

What about other, newer agents with chemotherapy? Amivantamab has hitched itself to chemotherapy. A trial in EGFR Exon 20 compared chemo to Amivantamab plus chemotherapy. There again, chemo is the common denominator. Amivantamab added approximately 5 months of improved progression-free survival. Again, chemo was used. In adjuvant, neoadjuvant, and targeted therapies, chemotherapy adds.

What about the second line? Everybody was very disappointed when second-line Sotorasib gave a very tiny amount of progression-free survival improvement over Docetaxel. Doctors want more for their patients than they can deliver with Docetaxel. The roughly 5-week improvement seen with Sotorasib was one that raised a question about the place of Sotorasib in this setting.

Clearly, it’s seen patients have an excellent result with Sotorasib as an additional option for treating patients with long progression-free survival, high rates of response, and good tolerability even at the 960 mg dose. But in the randomized trial, it wasn’t better than Docetaxel. Again, doctors were disappointed with Tusamitamab Ravtansine in that it could not beat Docetaxel either. I think the idea here is that chemo still has a huge place and still remains the treatment that have to beat.

All are excited about the antibody-drug conjugates and everybody sees them as another advance. Many folks have said that they are just a more precise way of delivering chemotherapy, and when you look at the side effects, it supports that — they’re largely side effects of chemotherapy with these drugs across the board. Also, when you look at the patterns of resistance, the resistance really isn’t a resistance to the targeted therapy; it’s a resistance to chemotherapy more than anything else.

So doctors are happy that the antibody-drug conjugates are available and they were disappointed with Tusamitamab Ravtansine because they thought that it beat Docetaxel. But in truth, it didn’t, and unfortunately, that pivotal trial led to the end of the entire development program for that agent, as stated in a press release.

The molecule or treatment of the year is chemotherapy — added to targeted therapies, used with immunotherapy, and now attached to antibodies as part of antibody-drug conjugates. It remains, more than any one treatment, a very effective treatment for patients and deserves to be used.

There are a lot of choices here. Doctors have to be very careful to choose wisely, and one have to be careful because chemotherapy has side effects. The nice thing is that many of those side effects can be ameliorated. Doctors have to make sure that they use all the supportive medications they can.

Who would have thought that chemotherapy would be the treatment of the year in 2023 for lung cancers?

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.