Pfizer Inc. (PFE -0.06%) already markets the $600-million-per-year lung cancer drug Xalkori, and next year, it could have two more lung cancer drugs on the market. Recently, Pfizer filed for FDA approval of lorlatinib and dacomitinib, two drugs targeting hard-to-treat lung cancer cases. If these drugs are approved, it could improve patient outcomes and add meaningfully to Pfizer's sales, so let's learn more about them. 

Second-line for now, but first-line is a possibility

First up is lorlatinib, a drug that's under review as a treatment for patients with ALK-positive metastatic non-small-cell lung cancer (NSCLC) who have progressed on one or more prior ALK tyrosine kinases inhibitors (TKIs). These treatment-resistant patients have few treatment choices and, unfortunately, face a poor prognosis.

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In February, the FDA accepted Pfizer's lorlatinib application for approval, granting it a priority review that shortens the regulatory review period to six months, from 10 months.

The priority review is supported by lorlatinib's impressive phase 2 results. In trials, 69% of patients previously treated with Xalkori responded, and 33% of patients who had been treated with an ALK inhibitor other than Xalkori responded to lorlatinib. Additionally, there was a 39% response rate in heavily pretreated patients who had received two or three prior ALK-inhibitors. If the FDA grants lorlatinib an approval based on these results, it could become an important new weapon in resistant ALK-positive metastatic NSCLC.

However, the drug's potential might not be limited to that patient population. Pfizer thinks it could be an effective first-line treatment. In phase 2 studies, the overall response rate in previously untreated patients was 90%, and the rate was 75% in patients with brain metastases. A phase 3 trial that could confirm those findings is already underway.

The addressable patient population targeted by lorlatinib is relatively small because ALK gene rearrangements only occur in up to 5% of NSCLC tumors. Yet, this could still be an important new drug for Pfizer because these patients have some of the poorest prognoses.

It bests a competitor, but question marks remain

After previously failing to outperform Tarceva in phase 3 trials back in 2014, dacomitinib delivered the goods last year against Iressa, another drug that's commonly used in the first-line to treat people with epidermal growth factor receptor (EGFR) positive lung cancer. In lung cancer, EGFR mutations can contribute to cancer cell growth and division; about 15% of NSCLC patients have EGFR mutations. 

In a head-to-head trial against Iressa, Pfizer enrolled a subgroup of people with EGFR-activating mutations that it saw as most likely to respond to dacomitinib. All of the patients participating in the trial were newly diagnosed with stage 3b/4 EGFR-positive NSCLC, and none had yet to receive a prior systemic therapy, including TKIs such as Tarceva.

In the trial, dacomitinib and Iressa produced similar overall response rates and each delayed disease progression similarly at the six-month mark. However, at 24 months, 30.6% of dacomitinib patients were still progression-free compared to only 9.6% of Iressa patients. Progression-free survival was a median 14.7 months for dacomitinib patients, and it was a median 9.2 months for Iressa patients.

Based on that performance, the FDA's giving dacomitinib a priority review, too, and if the agency gives it a green light, oncologists could use it instead of Iressa in the first-line setting. Iressa produced $528 million in sales for AstraZeneca last year, so dacomitinib's opportunity appears to be meaningful.

It does remain to be seen, however, how oncologists will view dacomitinib relative to other first-line treatment options in EGFR-positive lung cancer patients. As I mentioned, dacomitinib failed to outperform Tarceva, and AstraZeneca is already prioritizing another of its drugs, Tagrisso, over Iressa in this patient population. Also, while dacomitinib extended progression-free survival longer than Iressa, it did so with more toxicity. In its trial, 66% of patients required a dose reduction, compared to 8% for those in the Iressa side of the study.

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What to watch next

A decision from the FDA on lorlatinib in treatment-resistant ALK-positive patients is anticipated in August 2018, and a decision on dacomitinib as a first-line treatment in EGFR-positive patients is expected in September 2018. There's no guarantee these drugs will win an FDA go-ahead, but there's a big need for new drugs in this indication, and that could work in Pfizer's favor. If these drugs are approved, there's reason to think that both drugs could add nine figures in sales to Pfizer's top line. More than 230,000 new cases of lung cancer are diagnosed in the U.S. every year, and 85% of those cases are NSCLC.