Experimental drug fights lung cancer in nonsmokers: ‘I feel like I did when I was healthy’

Almost two years ago, Mireya Soriano, an Argentine engineer, writer and journalist, completely lost her appetite. Her strength drained away, and she began to feel severe pain in her right side. At La Paz Hospital in Madrid, where she has lived for more than a decade, she was told she had lung cancer that had spread to her liver. It seemed impossible: she had never smoked in her life.

At 76, Soriano embodies a growing phenomenon. Due in part to the success of global anti-smoking measures, fewer people are smoking, and lung cancer is declining among smokers, who account for approximately 80% of all cases. In return, oncologists are seeing a rise in this respiratory tumor in people who have never smoked. It’s a cancer that affects women more frequently, although it’s not clear why.

Doctors told Soriano that her prognosis wasn’t good. The tumor was a little-known subtype for which conventional treatments don’t usually work well. They recommended she go to 12 de Octubre Hospital, south of the capital, where a clinical trial had been launched with a new drug that might work. In November 2023, she was accepted into the trial, still so weak she could barely walk. She had lost 15 kilograms (33 lb).

A few weeks after starting treatment, Soriano entered a theater in Montevideo, Uruguay, to collect the Morosoli Silver Award for her literary work. “My son was in the audience and shouted, ‘Good job, Mom!’” explains the writer, sitting in a meeting room at the Madrid hospital. “Everyone probably thought it was because of the award, but it was really because I was able to climb the stairs all by myself,” she adds with a laugh. The writer jokes about being a “guinea pig.” She acknowledges that she has regained her strength and is returning to a normal life: “I feel like I did when I was healthy.”

Sitting next to her, her oncologist Jon Zugazagoitia, a 41-year-old from Spain’s Basque region, explains that Soriano’s response to treatment has been particularly good, but not exceptional. Doctors in the clinical trial, conducted in eight countries with 130 patients, detected tumor shrinkage in seven out of 10 participants.

The experimental drug that Soriano received is called zongertinib, and it’s part of a new generation of targeted therapies against tumors that exhibit certain genetic markers. In this case, it’s a mutation in the HER2 gene, which is present in approximately 3% of lung cancer cases. It may not seem like much, but in a country like Spain, with a population of approximately 48 million, that number accounts for approximately 900 people each year. The drug appears to work best in patients who, like Soriano, had not received other prior treatments such as chemotherapy or immunotherapy. The treatment is also easy to administer: one pill a day. The results of this trial, still preliminary, have been published in the New England Journal of Medicine, one of the most prestigious medical journals in the world.

These results are “encouraging,” Zugazagoitia argues, because until now there have been no effective treatments for this type of lung tumor, which is quite aggressive and in many cases is detected already with metastases to the liver or brain. Of the 30,000 cases of non–small-cell lung cancer (NSCLC) detected in Spain each year, about 6,000 are in non-smokers, and more than 60% are women.

The causes of this cancer are not entirely clear. It is partly due to genetics, and partly due to exposure to environmental agents such as radon — a toxic gas associated with granite — and air pollution. In 2023, a study revealed that just three years of breathing polluted air is enough to cause the incidence of lung cancer in nonsmokers to skyrocket.

Zugazagoitia recalls that his first experience with this type of tumor was in 2005, when he was still a resident physician. It was during those years that it was observed for the first time that this cancer subtype presented molecular alterations that could be a target for targeted therapies. A few years later, the first drug of this type arrived, targeting the EGFR mutation, and then others for ALK arrived. The trial with the new drug showed an average survival rate of 15 months, although the data could end up being much better, explains Zugazagoitia. “In the case of treatments targeting ALK, the initial data was similar, and now we’re already at five years,” he explains.

Most of the patients who will participate in the final phase of trials of the new drug, developed by the German pharmaceutical company Boehringer Ingelheim, have already been recruited and will begin testing in several countries this fall. The compound’s effectiveness will now be compared with the best available treatments. If the preliminary data are confirmed, zongertinib will join the other already approved targeted cancer drugs that are gaining ground in the battle against cancer.

“Currently, half of all patients with non-small cell lung cancer have some molecular alteration that we can treat with targeted treatment. Five years ago, it was only one in 10,” explains Zugazagoitia, head of the tumor microenvironment and immunotherapy group at the i+12 Research Institute, affiliated with the 12 de Octubre Institute.

The oncologist warns that we must be realistic about the potential of these drugs. Lung tumors remain the leading cause of cancer death worldwide, and the cases in which they are cured are still a minority. New treatments targeting genetic alterations reduce the size of tumors, even those that metastasize, but do not eliminate all malignant cells, warns Zugazagoitia. “Unfortunately, we are not there yet, but we started from a much worse situation, one in which we could do nothing. Although we cannot eliminate the disease, it is possible to make it chronic, and patients like Mireya, under treatment, can lead normal lives,” he argues.

The oncologist Rosario García-Campelo, a board member of the Spanish Society of Medical Oncology, admits that lung tumors in non-smokers still present many scientific unknowns. “We are seeing an increase in this cancer in the comparatively younger female population. This is now the fifth most deadly tumor worldwide,” she explains. The oncologist points to a possible role of estrogen and other female hormones in the development of these cancers, although this remains to be confirmed. García-Campelo believes that the new drug against HER2 “takes a giant step forward in the management of these patients.”

Mireya Soriano has had her cancer under control for over a year and a half. She hasn’t stopped writing articles for newspapers such as La Mañana in Uruguay. Last year she published Desde el Silencio (From Silence), a biography of Eduardo Strauch, a survivor of the 1972 Andean plane crash portrayed in films such as The Society of the Snow. She goes to the hospital every two weeks for tests, so far without any incidents. She is already writing her new novel, which is set in 1970s Argentina and which, for now, is going to be titled Con el Favor del Tiempo (With the Favor of Time).

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